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T Gross

Publications and source records attributed to T Gross.

At least 37 records · Page 2Linked to original sources
PubMed2001

Identification of TIA-1+ and granzyme B+ cytotoxic T cells in lichen sclerosus et atrophicus.

BACKGROUND: The onset and persistence of cutaneous lichen sclerosus et atrophicus (LSA) are linked to the presence of an inflammatory infiltrate of CD3+ T cells that includes CD4+ and CD8+ cells. The functional relevance of the presence of these cells is unknown. OBJECTIVE: The study intended to quantify resting and activated cytotoxic T cells in LSA lesions. METHODS: Twenty patients with active LSA were studied. Skin-infiltrating T cells were immunohistologically characterized with antibodies against CD3, CD8, T-cell-restricted intracellular antigen (TIA-1) and granzyme B (GrB). TIA-1 labels cytotoxic granules of resting and activated T cells, whereas GrB designates activated cytotoxic T lymphocytes (CTL). RESULTS: In all cases, numerous T cells were consistently found expressing cytotoxic granules. The results indicated a high number of infiltrating CD8+ TIA+ T cells. Furthermore, a notable number of GrB+ activated CTL associated with hydropic degeneration of the basal cell layer were found within the dermal infiltrate and at the dermoepidermal interface. CONCLUSION: This study shows that a high proportion of skin-infiltrating T cells in LSA has a potential cytotoxic function. The results indicate that hydropic degeneration of basal keratinocytes may at least partially be mediated by CTL-dependent mechanisms. Our data also indicate that a cell-mediated immune response may play an important role in the pathogenesis of the disease.

Adult↗
PubMed2000

First observation of different diffusion coefficients for two conformers in a neat liquid.

Self-diffusion coefficients were studied for the highly polar liquid N-methylformamide at pressures up to 200 MPa between the melting pressure curves and 420 K by the spin-echo method. N-Methylformamide exists as a mixture of two conformers in the neat liquid. These conformers have large differences at lower temperatures in their dynamic and structural properties. The self-diffusion coefficient of the cis-conformer being 17% lower than that of the trans-conformer at the same T and p. This is the first observation of such an effect. The experimental study is supported by Monte Carlo (MC) calculations which show that the first neighbors around a cis conformer are arranged differently than in an all trans liquid. The difference leads in the simulations to a much lower dielectric constant for the trans-cis mixture and might also explain the retardation of diffusion for the cis conformer.

Diffusion↗
PubMed2000

Attitudes of hospital staff involved in organ donation to the procedure.

Hospital staff have a key function in asking for potential organ donors, but little is known about their own attitudes towards donation. In a community hospital with 7-8 multi-organ extraction procedures each year 199 staff members were surveyed. Although only 7% of the responding staff would personally refuse to donate an organ, 23 % would not give consent to organ donation from a close relative. 47 % of those prepared to be donors had signed a donor card. Donors informed their family more frequently (88 %) about their personal attitude towards organ donation than non-donors (60 %), or undecided personnel (43,8 %; chi-square P = 0,004). No significant difference in attitude according to medical profession subgroups was found. The findings are in line with general population surveys and indicate that much work needs to be done to encourage medical staff involved in organ donation to set an example to the community.

Adult↗
PubMed2000

Transmission of viruses via contact in ahousehold setting: experiments using bacteriophage straight phiX174 as a model virus.

Contamination of the environment with pathogens is the prerequisite for contact infections. The aim of this study was to elucidate how viruses can be transmitted from a primary contact person to further individuals. Bacteriophage straight phiX174 was chosen as a model virus. In its stability straight phiX174 is comparable with the most resistant human pathogenic viruses, e.g. polio- or parvoviruses. About 10(7)pfu were applied to exposed contact points such as door handles or the hands of volunteers. After touching of these handles and common social contacts like hand shaking, re-isolation rates were determined from the hands of our test persons. Contaminated door handles and skin surfaces were found to be efficient sources for potential infection. At least 14 persons could be contaminated by horizontal spread, one after the other by touching the same door handle. Successive transmission from one person to another could be followed up to the sixth contact person. These results were confirmed under everyday life conditions in a flat shared by four students. The transmission could not be prevented by the usual standards of hand hygiene, practised in this household. straight phiX174 could be reisolated after 24h from the hands of all persons tested even after normal use and cleaning of their hands. This might be improved by the use of liquid soap dispensers.

Bacteriophage phi X 174↗
PubMed2000

Molecular epidemiology of EBNA-1 substrains of Epstein-Barr virus in posttransplant lymphoproliferative disorders which have infrequent p53 mutations.

Posttransplant lymphoproliferative disorders (PTLDs), which are highly associated with Epstein-Barr virus infection, have a low frequency of molecular genetic abnormalities. Recently it has been suggested certain EBV substrains may be associated with specific lymphoma subtypes. The goals of our study were two fold: 1) to determine the prevalence of EBNA-1 substrains and prognostic utility in PTLD and 2) to determine the incidence of p53 gene mutations and p53 protein overexpression in 32 EBV-positive PTLD cases. Tumor DNA was sequenced to identify EBNA-1 substrains at codon 487 and p53 gene mutations in exons 5-8. The PTLD samples contained the following EBNA-1 substrains: P-thr in 17/32 (53%), P-ala in 11/32 (34%), and V-leu in 4/32 (13%). More heterogeneity within major subtypes was seen in the PTLD cases than in the referral group. A second group of 25 referral (non-PTLD) samples including infectious mononucleosis (6) and sequential EBV positive virology samples (19) contained P-thr in 17/25 (68%); P-ala in 2/25 (8%); and V-leu in 6/25 (24%). In the 29 B-cell PTLD the time to presentation was an average of 13.3 months in the P-ala group, 16.6 months in the P-thr group, and 40.6 months in the V-leu group: (p>0.05). There was no difference in survival in patients (median overall--60 months) between the three different substrains of EBNA-1 (Log rank test, p=0.39). One of 31 (4.1%) cases (a diffuse large cell B-cell) had a p53 mutation. Seven of 31 (23%) cases (all B-cell), including the p53 mutated case, had over-expression of p53 protein. We conclude EBNA-1 substrains vary in PTLD and suggest the pattern reflects the geographical incidence of substrains in the region. We also conclude p53 mutations are not a significant molecular genetic abnormality in PTLD.

Epstein-Barr Virus Infections↗
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↗