Biomedical subjects
Publications and source records attributed to I Szilak.
We report the case of a 55-year-old man with neurosyphilis that presented with features of herpes simplex encephalitis. Neurosyphilis is easily diagnosed and treated and should be included in the differential diagnosis of herpes simplex encephalitis.
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The mechanics of chromosome movement, mitotic spindle assembly and spindle elongation have long been central questions of cell biology. After attachment in prometaphase of a microtubule from one pole, duplicated chromosome pairs travel towards the pole in a rapid but discontinuous motion. This is followed by a slower congression towards the midplate as the chromosome pair orients with each kinetochore attached to the microtubules from the nearest pole. The pairs disjoin at anaphase and translocate to opposite poles and the interpolar distance increases. Here we identify CENP-E as a kinesin-like motor protein (M(r) 312,000) that accumulates in the G2 phase of the cell cycle. CENP-E associates with kinetochores during congression, relocates to the spindle midzone at anaphase, and is quantitatively discarded at the end of the cell division. CENP-E is likely to be one of the motors responsible for mammalian chromosome movement and/or spindle elongation.
From a collection of monoclonal antibodies that specifically bind to various parts of the mitotic apparatus in human cells (1991. J. Cell Biol. 112: 1083-1097), two (1F1 and 1H1) recognize a greater than 200-kD intranuclear protein that associates with the spindle immediately upon nuclear envelope breakdown and progresses down the spindle microtubules to concentrate ultimately at the pericentrosomal region. At the completion of anaphase this protein dissociates from the spindle microtubules and is imported into the regenerating nuclei through the nuclear pores. Overlapping cDNA clones that span the entire length of the corresponding 7.2-kb mRNA reveal an encoded polypeptide of 236,278 D that is predicted to contain two globular domains separated by a discontinuous alpha-helix with characteristics for adopting a coiled-coil structure. The corresponding gene is highly conserved but neither the DNA sequence nor the predicted amino acid sequence shows significant homology to any previously reported. Since the cDNA also encodes the epitopes recognized by antibodies specific for two previously described proteins, NuMA and centrophilin, and all three show similar molecular weights and localization during the cell cycle, NuMA, centrophilin, and the 1F1/1H1 antigen represent either the same protein or a family of proteins, for which the original name, NuMA, seems most appropriate. While the function of NuMA remains uncertain, its unusual pattern of segregation at mitosis defines a novel pathway for the segregation of nuclear proteins during cell division.
Although cytoplasmic dynein is known to attach to microtubules and translocate toward their minus ends, dynein's ability to serve in vitro as a minus end-directed transporter of membranous organelles depends on additional soluble factors. We show here that a approximately 20S polypeptide complex (referred to as Activator I; Schroer, T. A., and M.P. Sheetz. 1991a. J. Cell Biol. 115:1309-1318.) stimulates dynein-mediated vesicle transport. A major component of the activator complex is a doublet of 150-kD polypeptides for which we propose the name dynactin (for dynein activator). The 20S dynactin complex is required for in vitro vesicle motility since depletion of it with a mAb to dynactin eliminates vesicle movement. Cloning of a brain specific isoform of dynactin from chicken reveals a 1,053 amino acid polypeptide composed of two coiled-coil alpha-helical domains interrupted by a spacer. Both this structural motif and the underlying primary sequence are highly conserved in vertebrates with 85% sequence identity within a central 1,000-residue domain of the chicken and rat proteins. As abundant as dynein, dynactin is ubiquitously expressed and appears to be encoded by a single gene that yields at least three alternative isoforms. The probable homologue in Drosophila is the gene Glued, whose protein product shares 50% sequence identity with vertebrate dynactin and whose function is essential for viability of most (and perhaps all) cells in the organism.
A cDNA encoding a specific form of thyroid hormone receptor expressed in human liver, kidney, placenta, and brain was isolated from a human kidney library. Identical clones were found in human placenta and HepG2 cDNA libraries. The cDNA encodes a 490-amino acid protein (Mr, 54,824). When expressed and translated in vitro, the protein product binds triiodothyronine with Ka of 2.3 X 10(9) M-1. This protein, designated human thyroid hormone receptor type alpha 2 (hTR alpha 2), has the same domain structure as other members of the v-erbA-related superfamily of receptor genes. It is similar to thyroid hormone receptor type alpha described in chicken and rat and less similar to human thyroid hormone receptor type beta (formerly referred to as c-erbA beta) from placenta. However, it is distinguished from these receptors by an extension of the C-terminal hormone binding domain making it 80 amino acids longer than rat thyroid hormone receptor type alpha 1 [Thompson, C.C., Weinberger, C., Lebo, R. & Evans, R. M. (1987) Science 237, 1610-1614]. Different sizes of mRNA found in liver (2.5 kilobases) and kidney (2 kilobases) suggest there may be tissue-specific processing of the primary transcript of this gene. Identification of human thyroid hormone receptor type alpha 2 indicates that two or more forms of thyroid hormone receptor exist in human tissues and may explain the normal variation in thyroid hormone responsiveness of various organs and the selective tissue abnormalities found in the thyroid hormone resistance syndromes.