Tolerance to IE molecules leads to deletion of V beta 17a-bearing T cells. Both, the CD4+ as well as the CD8+ T cell subsets are affected. A large percentage of CD4+ V beta 17a+ T cell hybrids recognize IE molecules. We now have investigated the reactivity for IE antigens of CD8+ V beta 17a+ T cell hybrids. Using a transfection approach, we have introduced the murine CD8 molecule into different V beta 17a+ T cell hybrids. Furthermore, the CD8 cDNA was transfected into the BW5147 alpha-beta- fusion partner. This allowed us to generate a large number of V beta 17a+ T cell hybrids by fusion with the appropriate T cells. Only 6% of T cell hybrids were stimulated to produce IL-2 upon incubation with IE+ cells. However, in those, the CD8 molecule seemed not to contribute to the IE reactivity of the hybrid, since mAbs against the CD8 molecule failed to inhibit their reactivity. This low percentage of V beta 17a+ CD8+ IE-reactive T cell hybrids contrasts with the strong reduction of CD8+ V beta 17a+ T cells in IE+ mice, strongly suggesting that elimination of such cells in the thymus occurs when they are coexpressing CD4 and CD8. This view was confirmed by the occasional expression of CD4 in some hybrids in which case IE reactivity was detected. Furthermore, we demonstrated the functional integrity of the introduced CD8 molecule by: (a) reconstitution of the IL-2 response in a class I-restricted TNP-specific T cell hybrid; and (b) by generation of alloreactive class I-restricted T cell hybrids using the new CD8+ fusion cell line. This CD8+ fusion partner, BWLyt2-4, should prove useful to study antigen processing and antigen presentation requirements of class I-restricted T cells.

Animals↗

PubMed1989

The human estrogen receptor has two independent nonacidic transcriptional activation functions.

We have previously reported the presence of a hormone-inducible transcriptional activation function (TAF-2) within the region of the estrogen receptor (ER) that contains the hormone binding domain. We show here that the N-terminal A/B region of the ER contains an independent constitutive activation function (TAF-1) that exhibits cell type specificity since it activates transcription efficiently in chicken embryo fibroblasts, but only poorly in HeLa cells. By analyzing the ability of TAF-1, TAF-2, and the GAL4 and VP16 acidic activating domains (AADs) to homosynergize and heterosynergize with one another and with the factor binding to the upstream element (UE) of the adenovirus 2 major late promoter, we show that the activation properties of TAF-1 and TAF-2 are different and distinct from those of AADs, in agreement with the absence of acidic amino acid stretches in TAF-1 and TAF-2.

Animals↗

PubMed1989

Achieve your targets.

Explore the source record for details and available documents.

Health Planning↗

PubMed1989

Two better cell lines for making hybridomas expressing specific T cell receptors.

Two variants of the AKR thymoma BW5147 have been isolated which can no longer express functional TCR alpha- and beta-chains. By generating hybridomas with these variant fusion lines, TCR of any normal T lymphocyte, including TCR-gamma/delta, can be studied at a clonal level, without interference of the BW5147-derived receptor chains. In this study one of the variants has been useful in identifying the reactivity to allogeneic MHC Ag of BW5147 itself.

Amino Acid Sequence↗

PubMed1989

36 cases of bites by spiders, including the white-tailed spider, Lampona cylindrata.

Thirty-six cases of bites by spiders are reported; in all cases, the spider was identified. No cases resulted in the formation of local ulcers, in necrosis, or in serious systemic symptoms. Eight bites by Lampona cylindrata, the white-tailed spider, caused a mild sting to sharp pain of short duration, itchiness, erythema, local swelling or a lump, and either no systemic symptoms, or anxiety. Five bites by Badumna insignis, the black house-spider, caused local pain, erythema, swelling, and no systemic symptoms, or anxiety, or chest pain and shortness of breath of mild degree and of short duration. The other spiders to be reported as causing bites were Hadronyche adelaidensis, Misgolas andrewsi, Aganippe subtristis, Olios calligaster, Isopeda pessleri, Eriophora sp., Phonognatha graeffei, Holoplatys sp., Breda jovialis, Opisthoncus sp., Lycosa sp. and Achaearanea tepidariorum.

Adolescent↗

PubMed1989

The V beta-specific superantigen staphylococcal enterotoxin B: stimulation of mature T cells and clonal deletion in neonatal mice.

Staphylococcal enterotoxin B is known to be a powerful T cell stimulant in mouse and man. In this paper we show that, for mice, this is because the protein in association with major histocompatibility complex class II molecules stimulates virtually all T cells bearing V beta 3 and V beta 8.1, 8.2, and 8.3, and few others. Neonatal mice given the enterotoxin eliminate all mature, and some immature, T cells bearing these V beta s, demonstrating that tolerance to exogenously administered antigen can be caused by clonal deletion of reactive T cells. The enterotoxin shares these "superantigenic" properties with known self-antigens in mice, Mls-1a and Mls-2a, and a B cell-derived product, a shared property that is unlikely to be coincidental or inconsequential.

Animals↗

PubMed1989

Molecular genetic analysis of 178 I-Abm12-reactive T cells.

We have studied the genetic diversity of the TCR repertoire to the murine alloantigen I-Abm12 by generating a panel of 178 C57BL/10-derived I-Abm12-reactive T cell hybridomas. The expression of V alpha and V beta gene families was examined in this panel and the frequency of expression of V beta, but not ofV alpha, gene families differed significantly from that observed in a companion panel of random C57BL/10-derived hybridomas. The V beta 5 gene family was expressed significantly less frequently while the V beta 14, V beta 15, and V beta 16 genes were expressed significantly more frequently in the panel of I-Abm12-reactive than in the panel of random hybridomas. The junctional regions (VJ alpha and VDJ beta) of TCR V alpha and V beta genes from selected I-Abm12-specific hybridomas were amplified using the polymerase chain reaction, and directly sequenced. Surprisingly, no conserved J alpha, D beta, J beta, or N region-encoded sequences among these selected I-Abm12-reactive TCRs were identified. Thus, the T cell response to an I-A alloantigen that differs by only three amino acid residues from the I-A molecule of the responding strain is genetically complex but nonrandom. We have estimated that the repertoire to this alloantigen is comprised of at least 37 different TCRs.

Amino Acid Sequence↗

PubMed1989

Effect of luminal perfusion rate on duodenal alkalinization in the rat in vivo and in vitro.

This study investigates the effects of luminal perfusion rate on the observed rate of alkalinization of an unbuffered saline by anesthetized rat distal duodenum. Increases in perfusion rate (range 0.3-22 ml/min) increased both alkalinization (3-15 mumol/cm hr) and intraluminal pressure (6-22 mm Hg). Increases in pressure (6-30 mm Hg) at constant perfusion rate (3 ml/min) did not change alkalinization. The effect of perfusion rate on alkalinization was rapid, reversible, and could be repeated several times. It was unaffected by indomethacin (10 mg/kg subcutaneously) or tetrodotoxin (1 mg/ml in perfusate). A limited in vitro study at two flow rates (0.3 and 22 ml/min) showed a similar enhancement of alkalinization. It is concluded that the rate of alkalinization is increased by raising the perfusion rate of the lumen both in vivo and in vitro. The mechanism remains to be established but may involve the reduction of a diffusion barrier between the mucosa and luminal bulk fluid. These results may have implications for the movement of other substances across intestinal segments.

Acid-Base Equilibrium↗

PubMed1989

Purification and properties of a procoagulant from peninsula tiger snake (Notechis ater niger) venom.

The procoagulant from Notechis ater niger was purified by gel filtration and anion exchange chromatography. It is a protein with an approximate mol.wt of 58,000 and in the presence of B mercaptoethanol is reduced to two chains with mol.wts of 37,000 and 23,000. The procoagulant has a pI of 7.3. The whole venom requires factor V to be present to bring about coagulation while Ca2+ and phospholipid are not essential, but when present stimulate this process. Normal prothrombin, but not decarboxyprothrombin, is converted by the venom. The activity of the procoagulant from Notechis species has been equated with factor Xa and in this study the similarity is noted, while ecarin-like characteristics in not requiring Ca2+ and phospholipid and an ability to clot heparinised plasma were also noted.

Anticoagulants↗

PubMed1989

A probe for intracellular concentrations of drugs: delayed fluorescence from acridine orange.

The aim of this work is to develop fluorescent probes that will indicate effective concentrations of therapeutic agents, or endogenous protectors, at important cellular sites. Acridine orange associates with nucleic acids and emits a 'delayed' fluorescence signal. This signal is quenched by oxidants such as oxygen, nitroaryl radiosensitizers, adriamycin and mitomycin-c, and reductants such as thiols, ascorbate and other radioprotectors. The quenching of the acridine orange delayed fluorescence reflects the effective concentration of these therapeutically-important oxidants and reductants near DNA. The relative concentration of basic radiosensitizers such as pimonidazole (Ro 03-8799) near the DNA is greater than that of misonidazole. Thiols quench the delayed fluorescence signal according to the degree of ionization of the thiol function; this may model the reactivity of thiols with guanine radical sites in DNA. Ascorbate and aminopyrine do not quench the delayed fluorescence from cells stained with acridine orange as these compounds are taken up by cells very inefficiently.

Acridine Orange↗

PubMed1989

The effects of the addition of nomegestrol acetate to post-menopausal oestrogen therapy.

Progestogens are added to the oestrogen treatment for 10-12 days each cycle in order to prevent endometrial abnormalities. However, concern has been expressed about the safety of certain of the currently available progestogens because of the potential adverse metabolic effects. We have evaluated the effects of nomegestrol acetate - non-androgenic progestogen - for administration to post-menopausal oestrogen users. Thirty-six (36) women receiving 50 mg oestradiol implants at regular intervals also took nomegestrol acetate for 12 days each calendar month at doses of 0.5 mg, 1.0 mg and 2.5 mg daily. Allocation to one of the dose regimens was random. Physical and psychological side-effects were recorded and all vaginal bleeding was noted: an endometrial biopsy was performed on the sixth day of progestogen addition for histological, ultrastructural and biochemical evaluation. Adverse side-effects were responsible for a dose-dependent drop out rates of 17%. All patients experienced a regular, progestogen-induced withdrawal bleed each month; and histological, ultrastructural and biochemical changes were induced within the endometrium by all 3 doses. Nomegestrol acetate is a potent progestogen and further studies are required to determine its lowest effective dose.

Adult↗

PubMed1989

c-myc oncogene expression and clinical outcome in carcinoma of the cervix.

The expression of the c-myc oncogene was studied in paraffin-embedded specimens of cervical biopsies using a monoclonal antibody which binds to the 62,000 Dalton protein encoded by the c-myc gene. A range of cervical cancers from intraepithelial neoplasia to advanced grade IV tumours were studied together with normal cervical biopsies; c-myc status was correlated to clinical progress. There was no correlation seen between the clinical stage of the disease at presentation and c-myc expression. The 15 patients with c-myc negative cervical cancers were shown to have better disease free (mean--95.4 mos) and total survival (mean 118.0--mos) compared to the 16 patients that were c-myc positive 28.4 and 48.4 mos respectively). The pattern of recurrence differed between the two groups with c-myc positive tumours more likely to develop extra pelvic metastatic disease. The c-myc status of cervical cancer offers a prognostic indicator that could be useful in guiding treatment decisions.

Female↗

PubMed1989

Soluble oil dermatitis: a review.

Cutting fluid technology has rapidly developed, presenting dermatologists and occupational physicians with a changing pattern of skin disease. The use of soluble oils has increased, and has been followed by an increase in the incidence of eczematous dermatitis. This is usually an endemic, chronic, irritant contact dermatitis, but thorough patch testing can also reveal allergic contact dermatitis. In conditions of heavy exposure, the prevalence of dermatitis can be as high as 30 per cent. Individual susceptibility is very variable. Research into resistance factors in those who do not develop dermatitis, and susceptibility factors in those who do, may elucidate basic mechanisms of irritancy. Efforts must continue to be directed at prevention because, once established, soluble oil dermatitis can be slow to resolve, even after specialist treatment and change of job. Prevention can be directed at the machine operative, the soluble oil, and the machine.

Dermatitis, Contact↗

PubMed1989

Preliminary study of the vascular dynamics of port-wine hemangioma with therapeutic implications for argon laser treatment.

The vascular dynamics of port-wine hemangioma have been studied in several ways in order to better understand blood flow factors. Utilizing a laser Doppler velocimeter, differential perfusion/blood flow was studied and contrasted to normal skin, compared to heat and cold challenges, and finally measured in relationship to argon laser treatment. Results indicate that port-wine hemangiomas do not necessarily have different perfusion than normal skin but respond less vigorously to heat challenges. Cooling showed no uniform response by port-wine hemangioma vessels, while injection with Xylocaine plus epinephrine resulted in a markedly decreased perfusion and vasoconstriction contrary to previously held theories. Argon laser treatment did not uniformly alter laser Doppler perfusion to a predictable degree. Laser Doppler velocimeter flow studies were not able to predict future good versus bad results of laser treatment.

Adolescent↗