Search PubMed⌕ Search

Biomedical subjects

C Jamieson

Publications and source records attributed to C Jamieson.

At least 37 records · Page 2Linked to original sources
PubMed1993

Photodynamic elimination of clonogenic Ph+ chronic myeloid leukemia cells.

Benzoporphyrin derivative (BPD) and light is a potent photosensitizer. We investigated this modality as a means to selectively eliminate clonogenic Ph(+) chronic myeloid leukemia (CML) cells. BPD at 10 ng/ml and 10.8 J/cm2 broad spectrum light eliminates from 5 to 6 logs of Ph(+) EM-2 cells. Long-term marrow culture studies of treated mixtures of normal and CML cells indicate that multipotent progenitor cell viability is retained while cells transcribing BCR-ABL are not detected. We conclude that BPD and light may offer a means of providing CML autografts potentially free of Ph(+) clonogenic cells.

Adult↗
PubMed1993

Magnetic resonance imaging in preoperative localization of diseased parathyroid glands: a comparison with isotope scanning and ultrasonography.

The value of magnetic resonance imaging (MRI) in the preoperative localization of parathyroid glands was assessed through a comparison of the findings with those obtained by ultrasonography and isotope scanning. The localization findings in 37 patients with primary hyperparathyroidism were compared with the operative findings. The sensitivities of the three modalities as defined by the ability to detect a parathyroid adenoma were 67% (isotope scanning), 44% (ultrasonography) and 36% (MRI). The differences were not significant. The sensitivities as defined by the ability to predict the correct side of the lesion were 48% (isotope scanning) 33% (ultrasonography) and 36% (MRI). No correlation was found between the sensitivity of a given localization test and factors such as the presence of thyroid abnormalities, size of the lesion, type of lesion and preoperative calcium and parathormone levels. The low sensitivity and high cost of all three preoperative localization studies render them unnecessary in the management of uncomplicated parathyroid disease. However, if preoperative imaging is necessary, ultrasonography and isotope scanning are recommended, since MRI was not found to be superior.

Adult↗
PubMed1993

Efficacy of benzoporphyrin derivative, a photosensitizer, in selective destruction of leukemia cells using a murine tumor model.

The ability of a photosensitizer, benzoporphyrin derivative monoacid ring A (BPD), and light to selectively kill leukemic cells in comparison to normal hemopoietic progenitors was investigated using a murine model, the L1210 tumor of DBA/2 mice. In vitro experiments indicated that treatment of cells with BPD and light effected a 5 to 6 log reduction of clonogenic L1210 cells under conditions which caused less than a 1 log reduction of committed myeloid progenitors, determined by colony-forming cells. This apparent therapeutic window was tested in vivo using lethally irradiated DBA/2 mice hematopoietically reconstituted with 10(6) syngeneic donor splenocytes or 5 x 10(5) bone marrow cells mixed with L1210 cells and treated with BPD and light. Reconstitution with 10(6) splenocytes resulted in successful engraftment of approximately 50% of recipients, indicating that these conditions provided limiting numbers of essential stem cells. The minimum tumor-eliciting dose was determined to be between 10(1) and 10(2) L1210 cells. Experiments in which 10(6) splenocytes were mixed with 10(6) L1210 cells and treated with BPD and light demonstrated that at 100 ng/mL of BPD and a specified light dose (5.4 joules [J]/cm2), 50% of recipients underwent successful engraftment and did not develop leukemic ascites. Animals that died under this regimen died from failure to engraft rather than from tumor burden. These results establish that this approach can effectively lower tumor burden by 4 logs with virtually no loss of essential hemopoietic progenitors. Similar results were obtained when animals received bone marrow rather than splenocytes.

Animals↗
PubMed1992

SALT trial.

Explore the source record for details and available documents.

Aspirin↗
PubMed1992

A T cell nuclear factor resembling NF-AT binds to an NF-kappa B site and to the conserved lymphokine promoter sequence "cytokine-1".

Nuclear extracts from a nontransformed murine T lymphocyte clone contained two inducible factors that bound to a nuclear factor kappa B (NF-kappa B) site. One factor was NF-kappa B, and the other was differentiated from NF-kappa B by its mobility in the electrophoretic mobility shift assay and its lack of sensitivity to protein kinase C depletion. Competition and methylation interference assays showed that the binding site for the novel factor was limited to nucleotides in the 3' half of the kappa B site. This part of the kappa B site resembled sequences in the binding site for a second inducible nuclear factor of T cells, NF-AT, as well as a conserved sequence found in several lymphokine genes, termed "cytokine-1" (CK-1). Competition and methylation interference analysis showed that both NF-AT and CK-1 sequences bound a factor similar to the novel kappa B-binding factor and that binding involved a four-nucleotide sequence (TTCC) that the kappa B, CK-1, and NF-AT sites have in common. The complexes that form with each site have characteristics of NF-AT: they are induced upon T cell receptor stimulation, are sensitive to protein synthesis inhibitors and cyclosporin A, and are not sensitive to protein kinase C depletion. Thus, a factor or factors similar to NF-AT can bind to three distinct promoter sequences which occur commonly in several T cell activation genes. These results raise the possibility that related factors binding to kappa B, CK-1, and NF-AT sequences could play a role in the coordinate induction of T cell activation genes. In addition, our results suggest that kappa B and CK-1 sites represent potential cyclosporin-sensitive promoter elements by virtue of their ability to bind an NF-AT-like factor.

Animals↗
PubMed1991

Physiologic activation of T cells via the T cell receptor induces NF-kappa B.

The transcription factor NF-kappa B has been implicated in the mitogen-induced expression of several genes that are critical for the immunologic function of T cells such as those encoding IL-2 and the IL-2R alpha chain (IL-2R alpha). We show here that NF-kappa B is induced in T cells activated by Ag, anti-CD3 antibody, or allogeneic stimulation. The induction of NF-kappa B via the TCR was dependent on protein kinase C. IL-2, which also activates IL-2R alpha expression and proliferation in T cells, was not able to induce NF-kappa B. TCR-mediated induction of NF-kappa B suggests a central role for this factor in activated T cells and also provides a mechanism for activation of latent HIV provirus during the normal immune response.

Animals↗
PubMed1991

Comparison of constitutive and inducible transcriptional enhancement mediated by kappa B-related sequences: modulation of activity in B cells by human T-cell leukemia virus type I tax gene.

The kappa B sequence (GGGACTTTCC) binds a factor, NF-kappa B, that is constitutively found in its functional, DNA binding form only in B lymphocytes. A factor with apparently indistinguishable sequence specificity can be induced in many other cell types, where it is used to regulate inducible gene expression. For example, kappa B-related sequences have been shown to be important for the transcription of a few inducible genes, such as the interleukin 2 receptor alpha-chain gene and the beta-interferon gene. However, these genes are not constitutively active in B lymphocytes, suggesting that other regulatory mechanisms must play a role in determining the patterns of expression. We have investigated the constitutive and inducible transcriptional activity mediated by five kappa B-related sequence elements in two different cell types. We show that in S194 plasma cells the activity of each element correlates well with the relative affinity of B-cell-derived NF-kappa B for that element. This leads to significantly lower transcription enhancement by sites derived from the interleukin 2 receptor or T-cell receptor genes in S194 cells. However, in either EL-4 (T) cells or S194 cells, both lower-affinity sites can be significantly induced by the tax gene product of human T-cell leukemia virus type I, showing that NF-kappa B activity can be modulated even in a B-cell line that constitutively expresses this factor.

Animals↗
PubMed1991

The prognostic importance of site and type of radiation-induced bowel injury in patients requiring surgical management.

A multivariate analysis was performed to determine the outcome, and factors prognostic for outcome, in 57 patients requiring surgical intervention for radiation bowel injury. The actuarial 2- and 5-year cause-specific survival (CSS) was 76 and 74%, respectively, with a median follow-up of 62 months for the survivors. The median time from surgery to death from complications was 4 months. Identified sites of injury were both large and small bowel. The types of injury were defined as stricture, perforation, inflammation, and fistula. At surgery 9 patients had more than one site, and 15 patients had more than one type of injury. Cox proportional hazards regression models relating survival to individual patient characteristics were constructed using surgical procedure, radiation-surgery interval, age, stage, radiotherapy technique and dose, and the individual sites and types of injuries. Only the site of injury was found to be of prognostic significance for CSS (P less than 0.03). However, when the site and type of injury were recoded as single or multiple, Cox regression analysis found both the site (P = 0.008) and the type (P = 0.02) of injury to be statistically significant for CSS (favoring single sites and types). Stepwise multivariate regression analysis found type of injury to be insignificant when site of injury was already in the model. Ileal damage was associated with the lowest CSS of any single site of injury (56%) and also appeared to be responsible for the poor CSS of those with multiple sites of injury (46%).

Adult↗
PubMed1991

Interleukin 2-activated killer cells do not mediate autologous thyrocyte lysis in autoimmune thyroid disease in vitro.

Because of interest in IL-2, and IL-2-activated killer cell-induced hypothyroidism in humans, we attempted to study an in vitro system that might prove to illuminate this disorder. We have thus studied interleukin 2 (IL-2--0, 12.5, 25, or 50 U/mL) activated killer cell-mediated autologous thyrocyte lysis, as well as cytotoxic activity in IL-2-stimulated mononuclear cell supernatants in 7 patients with autoimmune thyroid disease (2 Graves' disease and 5 Hashimoto's thyroiditis) using the 51Cr release assay. Controls included 14 patients with nonautoimmune thyroid disease (3 nontoxic goiter, 8 follicular thyroid adenoma, 2 papillary thyroid carcinoma, and 1 medullary carcinoma of the thyroid). Soluble IL-2 receptor (sIL-2R) in supernatants of peripheral mononuclear cells stimulated by IL-2 from these patients also was measured. Whereas in the control preparations, IL-2-activated killer cell activity was increased in a dose-dependent fashion relative to the IL-2 concentration, as well as to the effector cell/target cell ratio, in preparations from patients with autoimmune thyroid disease, this activity was not elevated as the IL-2 concentration was increased. The susceptibility of thyrocytes to the lytic effect of IL-2-activated killer cells was higher in controls than that in autoimmune thyroid disease (at concentrations of IL-2 of 0, 12.5, 25, and 50 U/mL) (p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Effects of recombinant human interleukin-2 and tumor necrosis factor-alpha with or without interferon-gamma on human thyroid tissues from patients with Graves' disease and from normal subjects xenografted into nude mice.

We have compared the effects of interleukin-2 (IL-2) or tumor necrosis factor-alpha (TNF alpha) administration with or without interferon-gamma (IFN gamma) on Graves' and normal thyroid tissue xenografts in the nude mouse (in the absence of an intact immune system) in terms of possible functional, immunological, or histological changes. The dosages of recombinant human IL-2, TNF alpha, and IFN gamma given to each mouse were 250, 800, and 4000 U, respectively; they were injected ip daily for 6 consecutive weeks. The parameters measured included the free T4 index, thyroid autoantibodies, and mouse TSH during the course of the study. Thyroid epithelial cell (TEC) HLA-DR expression was measured in thyroid tissue before xenotransplantation and at death; in addition, light microscopic studies were carried out at those times. There were no significant differences in thyroid function between the results in unstimulated (control) animals and those obtained with cytokine administration in either group of tissues, with the exception of the group receiving TNF alpha together with IFN gamma; in this latter group, the free T4 index declined significantly 4-6 weeks after commencement of treatment in the animals with normal thyroid tissue xenografts. The reduction of thyroid function induced by the combination of IFN gamma and TNF alpha observed in normal thyroid tissue may be due to inhibition of thyroperoxidase and thyroglobulin gene transcription. However, there was no such effect on the Graves' thyroid tissue xenografts, perhaps because of down-regulation of this tissue in response to cytokines, after having been released from long term in vivo immune stimulation. On the other hand, TNF alpha plus IFN gamma induced TEC HLA-DR expression on both types of thyroid xenografts at death, although IL-2 alone did not induce HLA-DR expression, and IFN gamma induced TEC significantly only on normal thyroid xenografts (but not on Graves' xenografts). In light microscopic examination, Graves' thyroid xenografts treated with IL-2 alone or TNF alpha plus IFN gamma appeared normal at death. In addition, normal thyroid xenografts treated with the same cytokines did not show discernible differences compared to those at human surgery or when the xenografts were untreated at death. We conclude that Graves' TEC did not differ from normal TEC in any significant fashion at the time of death, aside from a reduced responsiveness to the stimuli applied.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The effect of xenotransplantation of human thyroid tissue following radioactive iodine-induced thyroid ablation on thyroid function in the nude mouse.

We have attempted to determine whether xenotransplanted human thyroid tissue into nude mice would act as a physiological substitute for the mouse thyroid gland after the mice had been rendered hypothyroid, using radioactive iodine (131I). The dosage of 0.2 millicuries of 131I was given to each mouse. The xenotransplantations of human thyroid tissue, i.e., normal, Graves' and nontoxic multinodular goitre, were carried out three weeks after radioactive ablation. The values of TSH in all mice rose to high levels (71 +/- 15.6 ng/ml, +/- SD) by three weeks after 131I administration. The TSH values in the mice declined rapidly and reached normal levels by 3-5 weeks after xenotransplantation. In addition, the serum T4 values were generally in the euthyroid range by 3-6 weeks after xenotransplantation. There were no marked differences in the changes of serum T4 and TSH when the three groups were compared. These results indicated that the xenografted human thyroid tissue permitted a return to a normal feedback system as reflected by normal serum TSH and T4 values in the animals. The Graves' thyroid tissue reverted to normal physiological function when removed from its human (abnormal) immune environment, signifying that Graves' thyrocytes are mere passive captives to immune events. This model should prove to be useful in the study of human thyroid physiology and pathophysiology.

Animals↗
PubMed1990

Effects of recombinant human interferon gamma on human thyroid tissues from patients with Graves' disease and normal subjects transplanted into nude mice.

We have attempted to determine whether interferon gamma (IFN gamma) would enhance, sustain or induce autoimmune thyroid disease (AITD) in xenotransplanted thyroid tissue from patients with Graves' disease or normal persons (actually paranodular tissue) in nude athymic mice, in the absence of an intact immune system. A dosage of 4000 U/mouse of human IFN gamma (hIFN gamma) was injected intraperitoneally daily for six consecutive weeks into the xenotransplanted mice. The parameters measured included the free T4 index, thyroid autoantibodies and TSH during the course of hIFN gamma injections. Thyroid epithelial cell (TEC) HLA-DR expression was measured in the thyroid tissue before xenotransplantation and at sacrifice; in addition, light and electron microscopic studies were carried out at those times. There were no significant differences in thyroid function between the control results and those obtained with hIFN gamma in either group of tissues. TEC HLA-DR expression was significantly increased by hIFN gamma in the normal group, but insignificantly in the Graves' group. In both light and electron microscopic observations, Graves' tissue (whether or not treated with hIFN gamma) was indistinguishable at sacrifice from normal thyroid tissue. The appearance had markedly altered from the same Graves' tissue examined at the time of the initial human surgery, which then showed the usual histological appearance of this disorder. We conclude that IFN gamma induced HLA-DR expression alone is not sufficient to sustain the ongoing process of AITD in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Identification of a functional NF-kappa B binding site in the murine T cell receptor beta 2 locus.

We have identified a sequence in the TCR beta 2 locus that is homologous to the kappa B site in the Ig kappa light chain enhancer. This element, TCR beta-B, is located in the vicinity of previously identified T cell-specific DNase1 hypersensitive sites. Transfection analysis shows that a 60-bp fragment encompassing this site is preferentially active in T cells stimulated with phorbol esters or the HTLV-1 tax gene product compared with a B cell line that constitutively expresses NF-kappa B. Our results provide the first evidence for transcriptional regulatory sequences residing within the J beta 2-C beta 2 intron and suggest the possible involvement of these sequences in modulation of TCR beta gene expression upon cellular activation.

Animals↗
PubMed1989

The management of varicose veins.

The treatment of most of the complications of varicose veins lies in a knowledge of the pathophysiological mechanisms at work and the appropriate management of the veins themselves.

Diagnosis, Differential↗
PubMed1989

Nontoxic nodular goiter and papillary thyroid carcinoma are not associated with peripheral blood lymphocyte sensitization to thyroid cells.

We tested the claim that uni- and multinodular goiter (UNG and MNG) and papillary carcinoma (PC) of the thyroid are autoimmune thyroid diseases (AITD) similar to Graves' disease (GD) and Hashimoto's thyroiditis (HT). The expression of HLA-DR on cultured thyroid epithelial cells (thyrocytes) from UNG, MNG, and PC after coculture with autologous peripheral blood mononuclear cells (PBMC) was compared with that on GD and HT cells. The thyrocytes also were cultured with interferon-gamma (IFN gamma) alone. A cytotoxicity assay involving 51Cr-labeled thyrocytes, anti-HLA-DR, and complement was used to determine HLA-DR expression. Stimulation of thyrocytes with 200 U/mL IFN gamma induced HLA-DR (expressed as a cytotoxicity index) equally well on all thyrocytes [AITD (n = 6): IFN gamma, 23.8 +/- 7.7 (+/- SD); unstimulated, 3.6 +/- 2.0; UNG (n = 6), MNG (n = 9), and PC (n = 5): IFN gamma, 22.5 +/- 4.7; unstimulated, 4.0 +/- 3.0]. When cocultured with autologous PBMC, the values were: AITD, 24.9 +/- 10.1; UNG, MNG, and PC, 3.8 +/- 3.7 (P less than 0.001). The supernatants from the AITD cocultures had higher IFN gamma concentrations (by RIA) than those from the other cocultures. We conclude that in UNG, MNG, and PC, the peripheral blood helper T-lymphocytes are not sensitized to thyrocyte membrane antigen(s); consequently, little if any IFN gamma is produced in cocultures, and hence, there is no increase in thyrocyte HLA-DR expression, unlike the situation in AITD (GD and HT). Thus, UNG, MNG, and PC are not primarily autoimmune in nature, as defined by a lack of sensitization of the PBMC of such patients to thyroid antigen(s).

Antigens, Surface↗
PubMed1989

Pancreatoduodenal necrosis after endoscopic injection of cyanoacrylate to treat a bleeding duodenal ulcer: a case report.

N-butyl 2-cyanoacrylate monomer was injected at endoscopy in an attempt to control arterial bleeding from a duodenal ulcer crater. Segmental infarction of the duodenum and pancreatic head followed and necessitated pancreatoduodenectomy. Butyl 2-cyanoacrylate monomers have been used with angiography as embolization agents and with endoscopy to control variceal bleeding. To our knowledge, there are no reports of its use by endoscopic injection to stop arterial bleeding. Its potential for embolism in nonselective endoscopic injections may minimize the clinical application of butyl 2-cyanoacrylate monomers in the treatment of arterial gastrointestinal bleeding.

Cyanoacrylates↗