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Biomedical subjects

B Weinstein

Publications and source records attributed to B Weinstein.

At least 19 recordsLinked to original sources
PubMed1992

Microtubule assembly and phage morphogenesis: new results and classical paradigms.

The classical analyses of phage morphogenesis provide experimental paradigms for dissecting other assembly pathways. A new set of results, derived from examination of the quantitative controls of tubulin levels and microtubule assembly in Saccharomyces cerevisiae, evokes the 'balance of components' hypothesis. These results show that balanced levels of the tubulin proteins are crucial for microtubule assembly. Imbalances leading to excess beta tubulin have far more deleterious consequences than those leading to excess alpha tubulin, including dramatic cellular toxicity, quantitative depolymerization of cellular microtubules, and self-aggregation of the excess beta tubulin. These and other results suggest that beta tubulin may possess a unique ability to interact with a component of microtubule nucleating sites, and provide a rationale for the universal polarity of nucleated microtubules.

Bacteriophages↗
PubMed1990

Regulation of tubulin levels and microtubule assembly in Saccharomyces cerevisiae: consequences of altered tubulin gene copy number.

Microtubule organization in the cytoplasm is in part a function of the number and length of the assembled polymers. The intracellular concentration of tubulin could specify those parameters. Saccharomyces cerevisiae strains constructed with moderately decreased or increased copy numbers of tubulin genes provide an opportunity to study the cellular response to a steady-state change in tubulin concentration. We found no evidence of a mechanism for adjusting tubulin concentrations upward from a deficit, nor did we find a need for such a mechanism: cells with no more than 50% of the wild-type tubulin level were normal with respect to a series of microtubule-dependent properties. Strains with increased copies of both alpha- and beta-tubulin genes, or of alpha-tubulin genes alone, apparently did down regulate their tubulin levels. As a result, they contained greater than normal concentrations of tubulin but much less than predicted from the increase in gene number. Some of this down regulation occurred at the level of protein. These strains were also phenotypically normal. Cells could contain excess alpha-tubulin protein without detectable consequences, but perturbations resulting in excess beta-tubulin genes may have affected microtubule-dependent functions. All of the observed regulation of levels of tubulin can be explained as a response to toxicity associated with excess tubulin proteins, especially if beta-tubulin is much more toxic than alpha-tubulin.

DNA, Fungal↗
PubMed1990

Phenotypic consequences of tubulin overproduction in Saccharomyces cerevisiae: differences between alpha-tubulin and beta-tubulin.

Overexpression of alpha- and beta-tubulin genes in Saccharomyces cerevisiae, separately or together, leads to accumulation of large excesses of each of the polypeptides and arrest of cell division. However, other consequences of overexpression of these genes differ in several ways. As shown previously (D. Burke, P. Gasdaska, and L. Hartwell, Mol. Cell. Biol. 9:1049-1059, 1989), overexpression of beta-tubulin leads, at early times, to loss of microtubule structures and loss of viability. Eventually, the excess beta-tubulin forms abnormal structures. We show here that, in contrast, overexpression of alpha-tubulin led to none of these phenotypes and in fact could suppress each of the phenotypes associated with beta-tubulin accumulation. Truncated forms of beta-tubulin that were not competent to carry out microtubule functions also failed to elicit the beta-tubulin-specific phenotypes when overexpressed. The data support the hypothesis that beta-tubulin in excess over alpha-tubulin is uniquely toxic, perhaps because it interferes with normal microtubule assembly.

Base Sequence↗
PubMed1989

Neuromuscular and vascular hamartoma of the small bowel.

Neurovascular and muscular hamartoma is an unusual benign neoplasma of the small intestine. The clinical and pathological features of this lesion, which we recently encountered in a 91-year-old male, are the subject of this report and are discussed in the context of previously described cases.

Aged↗
PubMed1985

Recombinant human interferon sensitizes resistant myeloid leukemic cells to induction of terminal differentiation.

Recombinant human leukocyte interferon (IFN-alpha A) inhibits growth of the human promyelocytic leukemic cell line HL-60 without inducing these cells to differentiate terminally. When IFN-alpha A is combined with agents capable of inducing differentiation in HL-60 cells, such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA), cis or trans retinoic acid (RA) or dimethylsulfoxide (DMSO), growth suppression and induction of differentiation are dramatically increased. By growing HL-60 cells in increasing concentrations of TPA, RA, or DMSO, a series of sublines have been developed which are resistant to the usual growth inhibition and induction of differentiation seen when wild type HL-60 cells are exposed to these agents. Treatment of these resistant HL-60 cells with the combination of IFN-alpha A and the appropriate inducer results, however, in a synergistic suppression in cell growth and a concomitant induction of terminal differentiation. The ability of interferon to interact synergistically with agents which promote leukemic cell maturation may represents a novel means of reducing resistant leukemic cell populations.

Cell Differentiation↗
PubMed1983

Complete amino acid sequence of the light chain of human blood coagulation factor X: evidence for identification of residue 63 as beta-hydroxyaspartic acid.

The complete amino acid sequence of the light chain of human blood coagulation factor X has been determined by automated Edman degradation of peptides isolated from chemical and enzymatic digests of the carboxymethylated light chain. The protein consists of 139 amino acid residues, which include 11 residues of gamma-carboxyglutamic acid. The first 100 residues of the human factor X light chain exhibit approximately 80% homology when compared to the amino-terminal sequence of bovine factor X light chain. This homology decreases to approximately 50% in the remaining 39 residues of the carboxyl-terminal region of the protein. Proton nuclear magnetic resonance spectroscopy and mass spectrometry analyses of isolated residue 63 identified this residue as L-erythro-beta-hydroxyaspartic acid, a hitherto unrecognized amino acid in proteins. Evidence is also presented for the presence of this residue in the corresponding regions of the light chains of bovine factor X and bovine protein C. The biological function of beta-hydroxyaspartic acid in these proteins is unknown.

Amino Acid Sequence↗
PubMed1982

Structure of the Glycyl-L-histidyl-L-lysine--copper(II) complex in solution.

Optical, electron paramagnetic resonance, and electron spin-echo envelope spectroscopies were used to examine the structure of the Cu(II) complex of glycyl-L-histidyl-L-lysine (GHL) in solution. At neutral pH, GHL forms a mononuclear 1:1 Cu(II) compound having an EPR spectrum resembling that of Cu(II) equatorially coordinated by two or three nitrogen atoms. Electron spin-echo studies demonstrate that one of these is located in the histidyl imidazole ring. A pH titration of Cu(II)-GHL shows three optical transitions with apparent pKs of 3.6, 9.2 and 11.4 and molecularities, with respect to protons, of 2, 2, and 1, respectively. At the lowest pK, GHL binds Cu(II), forming the species present at physiological pH. At elevated pH, spectroscopic experiments suggest that an alteration of the Cu(II) structure occurs, yet the bound imidazole is retained. These solution studies are consistent with nitrogen coordination of Cu(II) in Cu(II)-GHL, but the solid-state polymeric structure, with oxygen-bridged Cu(II) pairs as previously determined by X-ray crystallographic analysis [Pickart, L., Freedman, J. H., Loker, W. J., Peisach, J., Perkins, C. M., Steinkamp, R. E., & Weinstein, B. (1980) Nature (London) 288, 715-717; C. M. Perkins, N. J. Rose, R. E. Steinkamp, L. H. Jensen, B. Weinstein, and L. Pickart, unpublished results], does not exist in solution.

Copper↗
PubMed1982

Avian vestibuloocular reflex: adaptive plasticity and developmental changes.

1. This study demonstrates plasticity of the vestibuloocular reflex (VOR) in chickens and compares it to that of other species and to that of newly hatched chicks. Adaptive changes in the VOR were induced by subjecting the animals to combinations of visual and vestibular stimuli that simulated the effect of the VOR being either too low in gain or reversed in phase. 2. The VOR of chickens resembles that of mammals, but the curve of phase lead versus frequency seems shifted toward higher frequencies. The VOR of newly hatched chicks has extremely low gain (less than 0.1). 3. In both the older and newly hatched animals, the VOR gain increased substantially after 2 h in an environment in which the imposed en bloc rotations produced increased retinal image slip in the normal directions. Similarly, 2 h of reversed retinal image slip produced decreased VOR gain and, in some cases, reversal fo the phase of the VOR. The gain changes were largest at the "training" frequency. The phase changes were in the direction of increased phase lead. Changes in the gains of the optokinetic responses and of the combination of VOR and optokinetic responses were also seen, especially in the newly hatched animals. 4. The newly hatched birds showed the largest VOR changes in the increased-gain situation, whereas the older birds showed the largest changes in the reversed-phase situation, as assessed by the changes in the average retinal slip velocity experienced. These results may well not be a consequence of differences in age, per se, but of differences in average retinal slip experienced in the two experimental situations at the start of the trial because of the lower VOR gain of the newly hatched animals. There seems to be no dramatic difference in VOR plasticity between newly hatched and older birds. 5. Our results with reversed visual motion are substantially different from those obtained in similar studies on rabbits, suggesting that these two species use different error signals to control the adaptive adjustment of the VOR.

Adaptation, Physiological↗
PubMed1981

Ultrasonography of partial hydatidiform mole.

Partial hydatidiform mole differs from complete mole by its focal distribution, its slower transformation, the presence of an embryo or fetus, and the triploid karyotype. Nineteen pathologically proved cases are presented. Partial mole can be diagnosed by a combination of the following sonographic findings: (a) greatly enlarged placenta relative to the size of the uterine cavity, (b) cystic spaces within the placenta ("molar placenta"), which may not always be present, (c) an amniotic cavity (gestational sac), either empty or containing amorphous fetal echoes, and (d) a well-formed but growth-retarded fetus, either dead or alive.

Abortion, Spontaneous↗