Search PubMed⌕ Search

Biomedical subjects

T Gross

Publications and source records attributed to T Gross.

At least 55 records · Page 3Linked to original sources
PubMed1996

Nitric oxide-independent inhibitory effects of L-arginine analog NG-monomethy-L-arginine on the generation of interleukin-2 activated cytotoxic activity in humans.

Nitric oxide (NO) derived intracellularly from L-arginine (Arg) is indispensable for optimalgeneration of lymphokine-activated killer (LAK) cell activity in rodents. Still unclear, however, is its role in humans. To address this question human peripheral blood mononuclear cells (PBMC) from healthy donors were cultured in L-arginine free medium supplemented with recombinant interleukin-2 (rIL-2) and in the presence of exogenous L-arginine analog NG-monomethyl-L-arginine (NMMA), a specific inhibitor of the NO synthetic pathway. Cultured PBMC were tested for cytotoxic activity, proliferative capacity, and expression of phenotypic and activation markers (CD3, CD4, CD8, CD16, CD56 and CD25). Culture supernatants were assayed for nitrite (NO2-) and tumor necrosis factor-alpha (TNF-alpha) production. We found that NMMA inhibits the generation of optimal LAK cell activity when no exogenous Arg is supplied. Similar effects were also observed on proliferation, expression of IL-2 receptor induced upon rIL-2 stimulation and on TNF-alpha production. Sodium nitroprusside (SNP), used as a source of exogenous NO could not overcome this effect of NMMA on LAK cell activity. NO2- production was virtually undetectable in culture supernatants. Thus, NMMA affects in an NO-independent manner rlL-2 induced LAK activity in human PBMC.

Journal Article↗
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↗
PubMed1994

Two genes encoding ribosomal protein L3 of Schizosaccharomyces pombe and their proximal promoter regions.

We have cloned and sequenced two genes, rpl3-1 and rpl3-2, encoding the ribosomal protein L3 of Schizosaccharomyces pombe. The two genes contain an open reading frame encoding 388 amino acids (aa) with a M(r) of 43,808. The aa sequences are identical, except at position 78, where Rpl3-1 displays a valine residue and Rpl3-2 contains isoleucine. The aa sequences show 75% identity to the RPL3 aa sequence from Saccharomyces cerevisiae. S1-nuclease protection analysis revealed that both genes are transcribed. The promoter sequences of the two rpl3 genes are significantly different, but both promoters contain the conserved homol-D element. Transcription starts between 40 and 50 nt downstream from this element.

Amino Acid Sequence↗
PubMed1993

[Incidence of ileus following rectum resection in rectal carcinoma with or without radiotherapy].

Between 1984 and 1989 240 patients underwent radical abdominal resection of a rectal carcinoma. Out of 201 patients surviving 12 months or more postoperatively, two groups are surveyed. The first group presents patients undergoing adjunctive radiation therapy (n = 47), while the second group did not undergo postoperative radiation therapy (n = 134). Mean follow-up time postoperatively is 39 months. Within the irradiation group, the incidence of ileus was found to be 23% (11/47), and in the non-irradiated group 8% (11/134). Subsequent reoperations in order to clear intestinal obstruction were performed on 4% (5/134) of non-irradiated patients and on 21% (10/47) of the irradiated group. Considering the increased risk of postoperative ileus after rectal resection for rectal carcinoma, serious reflection should be given to assessing the appropriateness of adjunctive radiation therapy.

Combined Modality Therapy↗
PubMed1993

The CAGTCACA box in the fission yeast Schizosaccharomyces pombe functions like a TATA element and binds a novel factor.

Fourteen ribosomal protein genes from the fission yeast Schizosaccharomyces pombe contain a highly conserved sequence, CAGTCACA, in the proximal promoter. This sequence, which was also conserved in its location, was found where the TATA element usually resides. Deletion and point mutations in the CAGTCACA box reduced the expression of these genes to almost zero and caused aberrant transcriptional start sites. Insertions between this box and the original transcriptional start sites led to new start sites which were the same distance from the CAGTCACA box as the original start sites. The results presented provide evidence that this box, like a TATA sequence, is involved in basal expression and fixing the transcriptional start sites of these genes. Furthermore, the CAGTCACA sequence is the target of a binding protein which appears to be different from the TATA-binding protein.

Base Sequence↗
PubMed1993

A new cardiotonic drug reduces the energy cost of active tension in cardiac muscle.

The novel thiadiazinone EMD 57033 (EMD) increases the calcium responsiveness of the contractile proteins in cardiac muscle. In skinned ventricular trabeculae isolated from guinea-pig heart, application of 10 microM EMD shifted the curve relating isometric tension to the applied calcium concentration to the left and increased maximal tension by 15%. In intact trabeculae, the rate of heat production, an indicator of the rate of ATP hydrolysis in the steady state, and isometric tension were measured at 37 degrees C. Both the thiadiazinone (EMD; 2.5, 5, and 10 microM) and the cardiac glycoside dihydro-ouabain (DHO; 5, 10, and 20 microM) produced a concentration-dependent increase in contraction-related heart production (Hc) and in the tension time integral of isometric contractions (Tti). In the presence of EMD the energy cost of active tension (Hc/Tti) was substantially decreased as compared to control conditions. The energy cost of the positive inotropic effect of EMD (43.8 mW N-1 cm-1) was only about half as large as the energy cost of the positive inotropic effect of DHO (88.4 mW N-1 cm-1). It is concluded that EMD causes a change in cross-bridge kinetics that increases the contractility of cardiac muscle and improves the economy of chemo-mechanical energy transduction. Our results suggest that EMD 57033 represents a prototype of a new class of cardiotonic agents that might be potentially useful in the therapy of congestive heart failure.

Animals↗
PubMed1993

Kinetic properties of the ATP-dependent actin-myosin sliding as revealed by the force-movement assay system with a centrifuge microscope.

To study the kinetic properties of the ATP-dependent actin-myosin sliding responsible for muscle contraction, we developed an in vitro force-movement assay system, in which centrifugal forces were applied to myosin-coated polystyrene beads sliding along actin cables of giant algal cells in the presence of ATP. Under constant centrifugal forces directed opposite to the bead movement ("positive" loads), the beads moved with constant velocities. The steady-state force-velocity (P-V) curve thus obtained was double-hyperbolic in shape, being analogous to the P-V curve of single muscle fibers. Under constant centrifugal forces in the direction of the bead movement ("negative" loads), on the other hand, the beads also moved with constant velocities. Unexpectedly, the velocity of bead movement did not increase with increasing negative loads, but decreased markedly (by 20-60%). We also studied the effect of centrifugal forces at right angles with actin cables on the bead movement.

Actins↗
PubMed1993

Essential role of myosin S-2 region in muscle contraction.

We studied the contraction characteristics and Mg-ATPase activity of glycerinated rabbit psoas muscle fibers in the presence and absence of polyclonal antibody directed against the subfragment-2 (S-2) region of myosin, to give information about the role of myosin hinge region in muscle contraction. The antibody was kindly supplied to us from Professor Harrington's laboratory. The antibody-induced decrease of Ca(2+)-activated isometric force development was always accompanied by a parallel decrease of muscle fiber stiffness, so that the stiffness versus force relation remained the same by the antibody treatment. Force-velocity curves, obtained by applying ramp decreases in load from steady isometric force to zero, indicated that the antibody had no effect on the maximum shortening velocity and the shape of the force-velocity curve. Simultaneous measurements of Mg-ATPase activity and Ca(2+)-activated isometric force showed that Mg-ATPase activity of the fibers remained unchanged despite the antibody-induced decrease of isometric force even to zero. These results indicate that, if the antibody attaches to the S-2 region of myosin molecules, their heads still hydrolyze ATP without contributing to both muscle force generation and muscle fiber stiffness.

Animals↗
PubMed1993

[The incidence of ileus after resection for rectal cancer with and without radiotherapy].

Between 1984 and 1989 240 patients had radical abdominal resection of a rectal carcinoma. Out of 201 patients surviving 12 months or more postoperatively, two groups are surveyed. The first group presents patients undergoing adjunctive radiation therapy (n = 47), the second group did not undergo postoperative radiation therapy (n = 134). Mean follow-up time postoperatively is 39 months. Within the irradiation group, the incidence of ileus was found to be 23% (11/47), in the non-irradiated group 8% (11/134). Subsequent reoperations in order to clear intestinal obstruction were performed on 4% (5/134) of non-irradiated patients and on 21% (10/47) of the irradiated group. Considering the increased risk of postoperative ileus after rectal resection for rectal carcinoma, serious reflection should be given to assessing the appropriateness of adjunctive radiation therapy.

Adult↗
PubMed1992

Contraction characteristics and ATPase activity of skeletal muscle fibers in the presence of antibody to myosin subfragment 2.

To investigate the role of the myosin hinge region in muscle contraction, we examined the contraction characteristics and Mg-ATPase activity of glycerinated muscle fibers prepared from rabbit psoas in the presence and absence of polyclonal antibody directed against the subfragment 2 (S-2) region of myosin. The antibody-induced reduction of Ca(2+)-activated isometric force was always accompanied by a parallel decrease of muscle fiber stiffness, so that the stiffness versus force relation remained unchanged by the antibody treatment. Force-velocity relations of the fibers, obtained by applying ramp decreases in force at steady isometric forces, indicated that the antibody had no effect on maximum shortening velocity or on the shape of force-velocity curves. Simultaneous measurements of Mg-ATPase activity and Ca(2+)-activated force showed that Mg-ATPase activity of the fibers remained unchanged despite the antibody-induced reduction of isometric force even to zero. These results indicate that when anti-S-2 antibody attaches to the S-2 region of myosin molecules, their heads still hydrolyze ATP but no longer contribute to both force generation and muscle fiber stiffness.

Animals↗
PubMed1992

[Incidence of ileus following rectum resection in rectal carcinoma with or without radiotherapy].

Between 1984 and 1989 240 patients underwent radical abdominal resection of a rectal carcinoma. Out of 201 patients surviving 12 months or more postoperatively, 2 groups are surveyed. The first group presents patients undergoing adjunctive radiation therapy (n = 47), while the second group did not undergo postoperative radiation therapy (n = 134). Mean follow-up time postoperatively is 39 months. Within the irradiation group, the incidence of ileus was found to be 23% (11/47), and in the non-irradiated group 8% (11/134). Subsequent reoperations to clear intestinal obstruction were performed in 4% (5/134) of non-irradiated patients and 21% (10/47) of the irradiated group. Considering the increased risk of postoperative ileus after rectal resection for rectal carcinoma, the appropriateness of adjunctive radiation therapy should be carefully assessed.

Adult↗