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T Gross

Publications and source records attributed to T Gross.

At least 19 recordsLinked to original sources
PubMed1999

Srp2, an SR protein family member of fission yeast: in vivo characterization of its modular domains.

We isolated srp2, a gene encoding a protein composed of two RNA binding domains (RBDs) at the N-terminus followed by an arginine-rich region that is flanked by two short SR (serine/arginine) elements. The RBDs contain the signatures RDADDA and SWQDLKD found in RBD1 and RBD2 of all typical metazoan SR proteins. srp2 is essential for growth. We have analyzed in vivo the role of the modular domains of Srp2 by testing specific mutations in a conditional strain for complementation. We found that RBD2 is essential for function and determines the specificity of RBD1 in Srp2. Replacement of the first RBD with RBD1 of Srp1 of fission yeast does not change this specificity. The two SR elements in the C-terminus of Srp2 are also essential for function in vivo. Cellular distribution analysis with green fluorescence protein fused to portions of Srp2 revealed that the SR elements are necessary to target Srp2 to the nucleus. Furthermore, overexpression of modular domains of Srp2 and Srp1 show different effects on pre-mRNA splicing activity of the tfIId gene. Taken together, these findings are consistent with the notion that the RBDs of these proteins may be involved in pre-mRNA recognition.

Alleles↗
PubMed1999

Prospective determination of distal colon findings in average-risk patients with proximal colon cancer.

BACKGROUND: Recent guidelines indicate that colonoscopy and sigmoidoscopy are both acceptable options for screening average-risk patients for colorectal cancer. Retrospective studies have found that a majority of patients with cancer proximal to the splenic flexure have a normal screening flexible sigmoidoscopy. METHODS: This was a multicenter, prospective description of colonoscopic findings and family history in consecutive patients with proximal colon cancer. RESULTS: Among 116 prospectively identified average-risk patients with cancer proximal to the splenic flexure, 40 (34.5%) had neoplasia distal to the splenic flexure. The prevalence of patients with adenomas greater than or equal to 1 cm, with only one tubular adenoma less than 1 cm, and with only hyperplastic polyps were 16.4%, 8.6%, and 6.9%, respectively. CONCLUSIONS: Most average-risk patients with cancer proximal to the splenic flexure will have a normal screening flexible sigmoidoscopy. These patients have an unexpectedly high prevalence of large distal adenomas, but the prevalence of both single small tubular adenomas and hyperplastic polyps alone is similar to that expected during screening of the general population. Clinicians and payers should continue to seek methods to improve the cost-effectiveness and availability of screening colonoscopy in average-risk persons.

Adenocarcinoma↗
PubMed1998

Cytoplasmic ribosomal protein genes of the fission yeast Schizosaccharomyces pombe display a unique promoter type: a suggestion for nomenclature of cytoplasmic ribosomal proteins in databases.

We identified 34 new ribosomal protein genes in the Schizosaccharomyces pombe database at the Sanger Centre coding for 30 different ribosomal proteins. All contain the Homol D-box in their promoter. We have shown that Homol D is, in this promoter type, the TATA-analogue. Many promoters contain the Homol E-box, which serves as a proximal activation sequence. Furthermore, comparative sequence analysis revealed a ribosomal protein gene encoding a protein which is the equivalent of the mammalian ribosomal protein L28. The budding yeast Saccharomyces cerevisiae has no L28 equivalent. Over the past 10 years we have isolated and characterized nine ribosomal protein (rp) genes from the fission yeast S.pombe . This endeavor yielded promoters which we have used to investigate the regulation of rp genes. Since eukaryotic ribosomal proteins are remarkably conserved and several rp genes of the budding yeast S.cerevisiae were sequenced in 1985, we probed DNA fragments encoding S.cerevisiae ribosomal proteins with genomic libraries of S.pombe . The deduced amino acid sequence of the different isolated rp genes of fission yeast share between 65 and 85% identical amino acids with their counterparts of budding yeast.

Amino Acid Sequence↗
PubMed1998

Identification and characterization of srp1, a gene of fission yeast encoding a RNA binding domain and a RS domain typical of SR splicing factors.

The SR protein family is involved in constitutive and regulated pre-mRNA splicing and has been found to be evolutionarily conserved in metazoan organisms. In contrast, the genome of the unicellular yeast Saccharomyces cerevisiae does not contain genes encoding typical SR proteins. The mammalian SR proteins consist of one or two characteristic RNA binding domains (RBD), containing the signature sequences RDAEDA and SWQDLKD respectively, and a RS (arginine/serine-rich) domain which gave the family its name. We have now cloned from the fission yeast Schizosaccharomyces pombe the gene srp1. This gene is the first yeast gene encoding a protein with typical features of mammalian SR protein family members. The gene is not essential for growth. We show that overexpression of the RNA binding domain inhibits pre-mRNA splicing and that the highly conserved sequence RDAEDA in the RBD is involved. Overexpression of Srp1 containing mutations in the RS domain also inhibits pre-mRNA splicing activity. Furthermore, we show that overexpression of Srp1 and overexpression of the mammalian SR splicing factor ASF/SF2 suppress the pre-mRNA splicing defect of the temperature-sensitive prp4-73 allele. prp4 encodes a protein kinase involved in pre-mRNA splicing. These findings are consistent with the notion that Srp1 plays a role in the splicing process.

Amino Acid Sequence↗
PubMed1998

Lupus humoral autoimmunity induced in a primate model by short peptide immunization.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by humoral autoimmunity against the spliceosomal proteins, including Sm B/B'. In SLE patients with anti-Sm B/B' antibodies the proline rich sequence, PPPGMRPP, is the predominant Sm B/B' autoimmune epitope and appears to be an early target in the development of the anti-Sm B/B' response. METHODS: Two female baboons were immunized with the PPPGMRPP peptide from the Sm B/B' spliceosomal protein constructed on a MAP backbone in Freund's adjuvant. One female control baboon was immunized with Freund's adjuvant alone. Baboon sera were collected and assessed for antibody binding to the spliceosomal proteins and compared to SLE patient and control sera. RESULTS: Peptide immunized baboons developed antibodies to multiple regions of the Sm B/B' protein, as well as reactivity against other spliceosomal proteins. Consistent with serologic manifestations found in SLE, experimental baboons also acquired anti-nuclear antibodies, anti-nuclear ribonucleoprotein (nRNP) antibodies and, in one animal, anti-double stranded DNA antibodies. The control animal had none of these immunologic findings. CONCLUSIONS: Immunization with PPPGMRPP is capable of initiating a humoral autoimmune response in primates against the Sm, nRNP complex from which the peptide was derived. The additional autoantibody specificities generated in experimental animals are similar to those found in human SLE sera. This study is the first evidence of peptide induction of SLE humoral autoimmunity in a primate model.

Amino Acid Sequence↗
PubMed1997

[How risky is lung resection today?--perioperative morbidity and mortality in open thorax surgery].

We retrospectively analyzed hospital morbidity and mortality following primary open lung surgery from August 1990 to December 1994 in 187 consecutive patients. 180 pulmonary resections and 7 exploratory thoracotomies were performed in 141 men and 46 women, with mean age 60.4 +/- 11.9 years. 142 patients were aged < 70 years (median 58.5), and 45 (25%) > 70 years (median 73). Tumor stage as well as preoperative ASA classification and FEV1 were similar in these age groups. No difference could be found in hospital morbidity of elderly compared to younger patients (> or = 70 years: 40%; < 70 years: 40.8%), but 30-day mortality was higher in elderly (8.9% versus 2.8% in younger subjects). Elderly patients who died postoperatively presented a higher preoperative risk (ASA 2.75) compared to nonfatal cases in the same age group (ASA 2.18). Morbidity and mortality increased with the extent of surgery; the 30-day mortality was nil in the group of wedge and segmental resections (0/23), 1.9% in lobectomies (2/106) and 7.8% in pneumonectomies (4/51). Our results in general match those of comparable centers in Switzerland and the international literature. Since the overall complication rate was not increased compared to younger patients, we assume that polymorbidity of single cases was the cause of higher mortality after extended open lung surgery in septuagenarians and octogenarians. In consequence, the scope of surgery should be reduced as far as possible. In addition, the perioperative risk for the senescent patient can be improved by identification of high risk cases. With this attitude we take the view that lung resection can honestly be recommended to the elderly also.

Adolescent↗
PubMed1997

Functional analysis of the fission yeast Prp4 protein kinase involved in pre-mRNA splicing and isolation of a putative mammalian homologue.

The prp4 gene of Schizosaccharomyces pombe encodes a protein kinase. A physiological substrate is not yet known. A mutational analysis of prp4 revealed that the protein consists of a short N-terminal domain, containing several essential motifs, which is followed by the kinase catalytic domain comprising the C-terminus of the protein. Overexpression of N-terminal mutations disturbs mitosis and produces elongated cells, Using a PCR approach, we isolated a putative homologue of Prp4 from human and mouse cells. The mammalian kinase domain is 53% identical to the kinase domain of Prp4. The short N-terminal domains share <20% identical amino acids, but contain conserved motifs. A fusion protein consisting of the N-terminal region from S. pombe followed by the mammalian kinase domain complements a temperature-sensitive prp4 mutation of S. pombe. Prp4 and the recombinant yeast/mouse protein kinase phosphorylate the human SR splicing factor ASF/SF2 in vitro in its RS domain.

Amino Acid Sequence↗
PubMed1997

Time-dependent decrease of presynaptic inotropic supersensitivity: physiological evidence of sympathetic reinnervation after heart transplantation.

BACKGROUND: Sympathetic cardiac denervation of the transplanted human heart causes a loss of the presynaptic neuronal uptake1-mechanism with consecutive supersensitivity to uptake1-dependent catecholamines. A return of neuronal function (reinnervation) should result in a decrease of supersensitivity to catecholamines subjected to this uptake system and thus may alter the inotropic regulation. METHODS: Inotropic dose-response curves were compared in 12 patients who were studied 3 to 15 months after transplantation (early) and 17 patients who were studied 23 to 156 months after transplantation (late) with isoproterenol (uptake1-independent) and epinephrine (uptake1-dependent). The inotropic response to increasing doses of isoproterenol (5 to 20 ng/kg per min) and epinephrine (10 to 40 ng/kg per min) was assessed with echocardiography as increase of the systolic pressure/dimension ratio (delta P/D) and of the rate-corrected velocity of circumferential fiber shortening (delta Vcfc). RESULTS: Inotropic dose/response curves to isoproterenol were identical in the early and late recipients (during 20 ng/kg per min. isoproterenol: delta P/D 2.07 +/- 1.36 vs 2.18 +/- 1.42 mm Hg/mm; delta Vcfc 1.55 +/- 0.33 vs 1.40 +/- 0.38 square root of min-1 x %/ms), indicating an unchanged inotropic effect mediated by the postsynaptic beta-receptor/effector system. However, the inotropic response to epinephrine in early recipients was significantly attenuated in the late recipients (during 40 ng/kg per min. epinephrine: delta P/D 3.35 +/- 2.06 vs 1.51 +/- 0.68 mm Hg/mm, p < 0.01; delta Vcfc 1.80 +/- 0.42 vs 1.05 +/- 0.35 square root of min-1 x %/ms, p < 0.001). CONCLUSIONS: These findings provide evidence for an at least partial restoration of the neuronal catecholamine uptake and are consistent with a time-dependent sympathetic reinnervation after heart transplantation. Restoration of neuronal uptake seems to be of functional importance, because it profoundly alters the inotropic effect of circulating endogenous catecholamines in long-term survivors after heart transplantation.

Adrenergic alpha-Agonists↗
PubMed1996

The recognition of human 60-kDa Ro ribonucleoprotein particles by antibodies associated with cutaneous lupus and neonatal lupus.

The hY RNAs form a macromolecular complex with the 60-kDa Ro protein and may in addition be bound by the La protein. In this study, we examine the autoantibody responses to the intact protein-RNA complexes in 18 subacute cutaneous lupus (SCLE), 10 discoid lupus (DLE), and 18 neonatal lupus erythematosus (NLE) sera. All SCLE and NLE serum samples precipitated all four of the Ro hY RNAs, whereas none of the DLE serum samples precipitated the hY RNAs. Among the SCLE and NLE sera, there was a significant association between the amount of Ro hY RNAs precipitated and the concurrent presence of anti-La antibodies in the sera (p = 0.008), consistent with the hypothesis that both the 60-kDa Ro and the La proteins can bind the Ro hY RNAs. There was no correlation between the amount of hY RNAs precipitated and the titer of antibodies to the 60-kDa Ro protein in enzyme-linked immunosorbent assay (ELISA). This may be due to a difference in the epitopes formed by the antigen in the respective assays. The autoantibody response to Ro in SCLE and NLE, which is generally detectable by both immunodiffusion and ELISA, is directed to all the subsets of the Ro protein-hY RNA complexes. The autoantibody response in DLE, though frequently detectable by ELISA, is not of sufficient concentration or affinity to precipitate the Ro protein-RNA complexes. The autoantibody response to Ro in SCLE and NLE may include antibodies to epitopes created by the complexing of the 60-kDa Ro protein with hY RNA.

Adult↗
PubMed1996

Differentiation of the bone-tissue remodeling response to axial and torsional loading in the turkey ulna.

The ability of bone tissue to differentiate between axial and torsional loading was determined with use of a functionally isolated turkey-ulna model of bone adaptation. Surface modeling and intracortical remodeling were quantified after four weeks of 5000 cycles per day of axial loading sufficient to cause 1000 microstrain normal to the long axis of the bone (five ulnae), 5000 cycles per day of torsional loading sufficient to cause 1000 microstrain of shear strain (five ulnae), or disuse (six ulnae). Of these three distinct regimens, only disuse caused a significant change in gross areal properties (12 per cent loss of bone; p < 0.05) as compared with those in the contralateral, intact control ulnae (sixteen ulnae). This finding suggested that both axial and torsional loading conditions were suitable substitutes for functional signals normally responsible for bone homeostasis. However, the intracortical response was strongly dependent on the manner in which the bone was loaded. Axial loading increased the number of intracortical pores by a factor of seven as compared with that in the controls (246 +/- 40.5 compared with 36 +/- 8.5 pores); it also increased the area lost because of porosis as compared with that in the controls (1.39 +/- 0.252 compared with 0.202 +/- 0.062 square millimeter); however, the mean size of the individual pores was similar to that in the controls (0.00565 +/- 0.0019 compared with 0.00561 +/- 0.0029 square millimeter). Conversely, torsional loading failed to increase substantially the number of pores (67 +/- 22.6 pores), the area of bone lost because of porosis (0.352 +/- 0.114 square millimeter), or the size of the pores (0.00525 +/- 0.0035 square millimeter) as compared with those in the controls. Although disuse failed to increase substantially the number of intracortical pores (59 +/- 22.4 pores), significant area (1.05 +/- 0.35 square millimeters; p < 0.05) was lost within the cortex because of a threefold increase in the mean size of each pore (0.0178 +/- 0.0126 square millimeter). It appears that bone tissue can readily differentiate between distinct components of the strain environment, with strain per se necessary to retain coupled formation and resorption, shear strain achieving this goal by maintaining the status quo, and axial strain increasing intracortical turnover but retaining coupling. While it is clear that load influences bone mass and morphology, it is also clear that specific parameters within the strain environment have distinct strategic roles in defining this architecture.

Adaptation, Physiological↗
PubMed1996

[Lung surgery in elderly patients--an increased risk?].

During 1990 to 1994, 180 pulmonary resections and 7 exploratory thoracotomies were performed and retrospectively analyzed for age-dependent hospital morbidity and mortality. Out of 141 men and 47 women (average age 60.4 +/- 11.9 years), 45 patients were 70 years or older (median 73 years). Mean ASA classification values were similar between patients under 70 years of age and the elderly (2.17 +/- 0.72), mean FEV1 was reduced in the group of old aged (2.45 +/- 0.61 vs. 2.71 +/- 0.82). No difference could be found in hospital morbidity of septuagenarians and octogenarians compared to younger patients (> or = 70 years: 40%; < 70 years: 40.8%), although hospital mortality increased in the elderly (11.1% vs. 3.5% in younger) with lethal cases presenting a higher preoperative risk rate (ASA 2.75 vs. 2.18). In conclusion, we did not experience an increased overall rate of complications after open lung surgery in the elderly, however, the risk of mortality increased in senescent patients with the appearance of a complication.

Aged↗
PubMed1995

The tandem repeat AGGGTAGGGT is, in the fission yeast, a proximal activation sequence and activates basal transcription mediated by the sequence TGTGACTG.

Ribosomal protein (rp) genes in the fission yeast Schizosaccharomyces pombe display two highly conserved sequence elements in the promoter region. The molecular dissection of these promoters revealed that basal transcription is not based on a TATA element. The sequence which promotes basal transcription is the conserved sequence CAGTCACA or the inverted form TGTGACTG, called the homol D box. Upstream of the homol D box a tandem repeat AGGGTAGGGT or the inverted form ACCCTACCCT appears in some promoters, called homol E. This element functions in the proximal arrangement with homol D as an activation sequence. A compilation of homol D and homol E sequences identified in other S.pombe promoters revealed that several putative polymerase II and polymerase III promoters display a homol D box or the homol E/homol D arrangement.

Base Sequence↗
PubMed1995

HLA-B27 binding of peptide from its own sequence and similar peptides from bacteria: implications for spondyloarthropathies.

The spondyloarthropathies are associated by an unknown mechanism with HLA-B27 and certain bacteria. HLA-B27 shares sequence with proteins from enteric bacteria. The B*2705 sequence contains a nonapeptide, LRRYLENGK, predicted to bind in the binding cleft of B27. Some nonapeptides from enteric organisms that share sequence with this nonapeptide of B27 also bind B27. These observations suggest an unappreciated mechanism for autoimmunity that may operate in the B27-associated spondyloarthropathies involving peptides bound to and derived from histocompatibility alleles.

Amino Acid Sequence↗
PubMed1995

Immunoglobulin epitope spreading and autoimmune disease after peptide immunization: Sm B/B'-derived PPPGMRPP and PPPGIRGP induce spliceosome autoimmunity.

Autoantibodies from many patients with systemic lupus erythematosus bind the Sm autoantigen B/B' polypeptide. The binding of serial serum specimens to the 233 overlapping octapeptides of Sm B/B' have shown that of the B/B'-derived octapeptides, PPPGMRPP and PPPGIRGP are early targets of the autoimmune response in some lupus patients. Rabbits immunized with PPPGMRPP and PPPGIRGP develop antibodies which not only bind these octapeptides, but also subsequently bind many other octapeptides of Sm B/B'. Eventually, the rabbits immunized with one octapeptide develop autoantibodies that bind other spliceosomal proteins including D, 70K, A, and C. Any mechanisms that operate to maintain tolerance or anergy for the spliceosome are thus overcome. Features considered typical of human systemic lupus erythematosus are also found in these peptide-immunized animals, such as antinuclear antibodies, anti-Sm precipitins, anti-double-stranded DNA, thrombocytopenia, seizures, and proteinuria. This disease model provides access to a mechanism for the development of humoral autoimmunity and may provide a basis to explain the immunopathogenesis of lupus in humans.

Amino Acid Sequence↗
PubMed1995

Effect of lateral forces on the movement of myosin-coated beads on actin cables studied using a centrifuge microscope.

We developed an in vitro motility assay system, in which myosin-coated polystyrene beads were made to slide on actin filament arrays (actin cables) in giant algal cells and subjected to centrifugal forces, which were parallel to the direction of bead movement to serve as external loads on actin-myosin sliding (Oiwa et al. (1990) Proc Natl Acad Sci USA 87: 7893-7897), and succeeded in determining the steady-state force-velocity relation of ATP-dependent actin-myosin sliding. To give further information about the properties of actin-myosin sliding, we have applied centrifugal forces, in parallel with the plane of actin-myosin sliding but at right angles with the direction of bead movement, and have found that such "lateral" centrifugal forces reduced the velocity of bead movement. In addition, we have also found that the velocity of bead movement is reduced more markedly with lateral forces applied from the left side of the bead ("left" lateral forces) than those applied from the right side of the bead ("right" lateral forces). These results are discussed in connection with the direction of sliding force generated by the myosin heads on the bead which interact with the right-handed double helix of actin monomers constituting actin filaments.

Actins↗