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Biomedical subjects

R Ware

Publications and source records attributed to R Ware.

At least 19 recordsLinked to original sources
PubMed2006

Family average income and diagnosed Type 2 diabetes in urban and rural residents in regional mainland China.

AIMS: To explore the relationship between family average income (FAI; an index of socio-economic status) and Type 2 diabetes in a region of mainland China. METHODS: Population-based cross-sectional study, conducted between October 2000 and March 2001 in administrative villages (n = 45) randomly selected from three urban districts and two rural counties of NanJing municipality, mainland China, with a regional population of 5.6 million. Participants were all local residents aged > or = 35 years old (n = 29 340); 67.7% from urban areas, 32.3% from rural areas, 49.8% male and 50.2% female. RESULTS: The response rate of eligible participants was 90.1%. The overall prevalence of self-reported Type 2 diabetes was 1.9%. After adjustment for possible confounding variables (age, gender, area of residence, body mass index, educational level, smoking status, occupational and leisure-time physical activity), participants in the higher and middle FAI categories were more than twice as likely to have Type 2 diabetes as those in the lower FAI category. CONCLUSIONS: The prevalence of Type 2 diabetes is positively related to socio-economic status (indexed by FAI) in Chinese at the population level. After controlling for potential confounding factors, people in higher socio-economic status groups are more likely to have Type 2 diabetes. These associations are consistent with other effects of epidemiological transition and identify a need for preventive initiatives.

Adult↗
PubMed2001

Imaging with F-18 FDG PET is superior to Tl-201 SPECT in the staging of non-small cell lung cancer for radical radiation therapy.

Thallium-201 (Tl-201) single photon emission computed tomography (SPECT) is funded for evaluation of malignancy in Australia and may have utility for staging of non-small cell lung cancer (NSCLC) if CT results are equivocal. Fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET) is superior to CT for staging NSCLC but is more expensive and less widely available than Tl-201 SPECT. Therefore, these techniques were prospectively compared in 27 radical radiation therapy candidates. Patients were allocated a conventional, PET and Tl-201 stage. Tumour to background ratios (TBR) were recorded for the primary on both techniques. Metastatic disease was confirmed by surgical pathology, serial imaging or clinical follow up. Tumour to background ratios were consistently higher for FDG PET than Tl-201 SPECT (P < 0.0001). Positron emission tomography detected all known primary tumours but Tl-201 failed to image four primary tumours (15%). In 10 of 18 cases of discordance between PET and Tl-201 SPECT regarding stage, corroboration was available from pathology or disease progression. Positron emission tomography was shown to have a 100% positive predictive value, including all three patients with PET-detected distant metastases (P=0.002). Results indicate that PET is superior to Tl-201 SPECT scanning in the staging of NSCLC for radical radiation therapy, and that the low sensitivity for detection of local and metastatic disease is likely to limit the clinical impact and cost-effectiveness of this technique despite its lower cost.

Aged↗
PubMed2001

The utility of a 3-dimensional, large-field-of-view, sodium iodide crystal--based PET scanner in the presurgical evaluation of partial epilepsy.

UNLABELLED: (18)F-FDG PET is an accurate and reliable technique for localizing medically refractory temporal lobe epilepsy, but widespread use has been hindered by limited reimbursement in many countries because of the high cost of traditional PET equipment and radioisotopes. Additionally, the place of FDG PET as a cost-effective tool for presurgical evaluation of epilepsy has been questioned because of limited data showing that FDG PET provides localization information incremental to that provided by more established techniques, particularly MRI and ictal electroencephalography (EEG). Three-dimensional (3D), large-field-of-view, sodium iodide crystal-based scanners have lower equipment and running costs and better multiplanar resolution than traditional 2-dimensional bismuth germinate (BGO) systems but have not yet been validated for evaluation of epilepsy. Our purpose was to investigate the localization rate, accuracy, and prognostic value of FDG PET images acquired on a 3D, large-field-of-view, sodium iodide crystal-based PET scanner in the presurgical evaluation of intractable partial epilepsy. We also wanted to establish the incremental value of FDG PET over established MRI and ictal EEG techniques. METHODS: Fifty-five patients who were surgical candidates because of medically refractory partial epilepsy were examined. For most of these patients, the lesions had not been clearly localized on conventional assessment. The FDG PET scans were reviewed independently by 2 reviewers who were unaware of the patients' clinical details, ictal EEG findings, and volumetric MRI results, and the FDG PET results were correlated with those of MRI and EEG and with postsurgical outcome. RESULTS: Forty-two patients (76%) had localizing FDG PET images (37 temporal, 5 extratemporal). The ictal EEG recordings were localizing in 66%, and the MRI findings were localizing in 27% (which increased to 35% after the MRI findings were reviewed again after PET). Concordance between the site of the PET localizations and the site of the MRI or EEG localizations was 100%. The PET images were localizing in 63% and 69% of patients with nonlocalizing ictal EEG and MRI findings, respectively. Twenty-one of 24 patients who subsequently underwent epilepsy surgery had localizing FDG PET images; of these 21 patients, 18 (86%) had a class I outcome. Multiple regression analysis showed the FDG PET results to be predictive of postsurgical outcome independently of the MRI findings. CONCLUSION: For intractable partial epilepsy, FDG PET using a 3D, large-field-of-view, sodium iodide crystal-based scanner provided clinically useful localizing information that was at least as accurate as the results reported for traditional BGO-based scanners. The PET images provided prognostically significant localization information incremental to that provided by volumetric MRI and ictal EEG, particularly if 1 of these studies was nonlocalizing.

Adolescent↗
PubMed2000

Preoperative sestamibi scanning and surgical findings at bilateral, unilateral, or minimal reoperation for recurrent hyperparathyroidism after subtotal parathyroidectomy in patients with multiple endocrine neoplasia type 1.

HYPOTHESES: Preoperative parathyroid radioisotope scanning is of little or no value in patients with multiple endocrine neoplasia type 1 when 4 or more hypertrophied glands are present. Scanning using technetium Tc 99m sestamibi and single photon emission computed tomography will achieve a high level of sensitivity and specificity after 3 or more glands have previously been removed, justifying limited surgical reexploration. DESIGN: In a prospective study, the preoperative documented report of the predicted site of residual parathyroid was compared with the surgical findings in 13 patients having 19 scans and 17 reoperations. SETTING: All patients belonged to one family, previously described as Tasman family 1, and were confirmed by genetic testing as having multiple endocrine neoplasia type 1. In 10 of 13 patients, reexploration was being undertaken more than 10 years after the first operation. MAIN OUTCOME MEASURES: Scanning was regarded as successful when the documented preoperative report correctly predicted the side and quadrant in which a gland was found at surgery. Surgery was regarded as successful when calcium levels decreased to or below normal levels and were maintained. RESULTS: All 13 scans before first reexploration were successful in identifying the location of a residual parathyroid. From a statistical viewpoint, this equates to 100% sensitivity and 92% specificity. However, despite accurate localization of 1 residual gland in every patient, 7 supernumerary glands in 4 patients and 1 parathyroid remnant in a fifth patient were not localized so that sensitivity in locating all glands in every patient was only 61%. Scans performed for persistent hypercalcemia 48 to 72 hours after reexploration in 2 patients were unsuccessful in demonstrating any residual parathyroid. Scans performed 3 months after surgery in the same 2 patients and a third patient were successful, with sensitivity and specificity of 100%. Apart from patient 11, who awaits reexploration, normocalcemia was eventually achieved in every patient, with 11 of 12 having an initial period of hypocalcemia. CONCLUSIONS: Three months after reexploration and trimming or resection with transplant of half a gland left at first operation, sestamibi scanning achieved sensitivity and specificity of 100% in locating supernumerary parathyroids in patients with multiple endocrine neoplasia type 1 and persistent hypercalcemia. Before first reexploration, however, scans rarely provided new information, predominantly showing only the hypertrophied half-gland remnant.

Adult↗
PubMed2000

29. F-18 FDG PET for Suspected or Confirmed Regional Recurrence of Colon Cancer. A Prospective Study of Impact and Outcome.

Purpose: Survival of patients (pts) undergoing "curative" treatment for colorectal carcinoma remains poor. Retrospective studies suggest that F-18 FDG PET is more accurate than CT for restaging suspected recurrent disease and favourably impacts management. The aim of this study was to confirm this by prospective analysis.Patient Population and Methods: 102 consecutive patients for whom the referring clinicians had prospectively committed to a treatment plan based on conventional staging investigations and who then underwent F-18 FDG PET scanning were evaluated for management change and outcome. The accuracy of PET results was assessed by surgical findings or clinical follow-up.Results: Overall PET changed management in 66/102 (65%) pts including14 pts changed from observation to active treatment after PET localized disease and 6 pts planned for local therapy to observation after negative PET. Planned surgery was cancelled in 28 pts whereas surgery was initiated in 11 pts. Radiotherapy was prevented in 5 pts, initiated in 11 and the radiation field altered in 5 others. The accuracy of the PET results could be assessed in 63/66 (95%) pts in whom management was changed. Relapse was confirmed in 50/51 pts with a positive PET but disease extent was underestimated in 4 cases. False negative PET results were confirmed in 5 cases.Conclusion: FDG PET has a high and appropriate impact on patient management in patients with suspected recurrent disease. PET can miss small volume disease but the major benefit of PET is to prevent futile attempts at local salvage therapies.

Journal Article↗
PubMed1999

A novel 26 kilodalton antigen expressed on the surface membrane of activated T cells.

We have identified and characterized the tissue distribution of the antigen recognized by a novel monoclonal antibody (mAb) 1B10, raised against an activated gammadelta T cell clone. Immunohistochemistry of tissue sections, and analysis of single cell suspensions by flow cytometry revealed that mAb 1B10 weakly reacted with <6% of normal human peripheral blood mononuclear cells (PBMC). After 5-6 days of in vitro culture of PBMC activated with phytohemagglutinin (PHA), 55% of the CD4+ and 25% of the CD8+ T cells became 1B10+. 1B10 expression was maintained on long term cultured interleukin 2 (IL-2)-dependent T cell receptor (TCR) alphabeta+ and gammadelta+ clones, and importantly, in contrast to resting T cells, the majority of in vivo activated synovial T lymphocytes from a patient with rheumatoid arthritis were 1B10+. In addition, myelo-monocytic U927 cells, tissue macrophages and some epithelia and fibroblasts were found to react with mAb 1B10. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of molecules immuno-precipitated by mAb 1B10 from radio-iodinated cell surface membrane lysates of T lymphocyte and U937 cells revealed 26 and 29 kiloDalton (kDa) glycoproteins respectively. In conclusion, mAb 1B10 recognizes a novel < > appearing 26 kDa T cell activation antigen that may be useful for further studies of activated T cells in health and disease.

Antibodies, Monoclonal↗
PubMed1997

Two families with an autosomal dominant inheritance pattern for papillary carcinoma of the thyroid.

BACKGROUND: Papillary carcinoma of the thyroid (PTC) is the most prevalent malignancy of the thyroid gland. Although the majority of lesions are sporadic tumors, an established relationship exists between familial adenomatous polyposis (FAP) and PTC. Moreover, some authors postulate the existence of familial PTC as a distinct entity. Evidence for this is limited, however, there being few well characterized descriptions of pedigrees with high prevalence of PTC. AIMS: The objective of the present study was to examine an apparent heritable predisposition to PTC occurring in two Tasmanian families in which PTC occurs commonly. METHODS: Pedigree charts were constructed for both families and the medical records of the members reviewed. RESULTS: In Pedigree I, 7 of 25 members had PTC (6 of these had coexisting multinodular goiter (MNG), and 11 others had MNG. In Pedigree II, identical male twins and their daughters had PTC. CONCLUSIONS: In both families there is evidence of autosomal dominant inheritance of PTC. The association of PTC with MNG suggests a possible role for MNG in tumor pathogenesis in hereditary PTC. The majority of the patients were diagnosed with PTC before commencement of prospective screening, indicating clinically relevant disease in the families described.

Adult↗
PubMed1996

Herpesvirus saimiri-transformed human CD4+ T cells can provide polyclonal B cell help via the CD40 ligand as well as the TNF-alpha pathway and through release of lymphokines.

We have developed human CD4+ T cell lines from the PBL of normal donors by infection with Herpesvirus saimiri (HVS), to evaluate functional properties of these immortalized lymphocytes. In this report, we characterize two such CD4+ T cell lines, CHCD4 and MHCD4, which were derived from two different donors. These cells grew independent of exogenous IL-2 stimulation for over 1 yr, and expressed surface markers (CD25+, CD69+, HLA-DR+, and B7+) associated with an activated T cell phenotype. Both lines constitutively produced and released IFN-gamma, but no IL-2 or IL-4. However, the surface expression of the two cell lines differed in that CHCD4 constitutively expressed CD40 ligand (CD40L) and membrane TNF-alpha, but MHCD4 did not. Also, CHCD4, but not MHCD4, potently induced polyclonal B cell activation and differentiation in the absence of PWM, in an MHC-unrestricted fashion. The B cell help afforded by CHCD4 included contact-dependent and soluble components. Contact-dependent help was strongly inhibited by mAb against CD40L (5C8) and to a lesser extent, by anti-TNF-alpha Ab. The CD40L-dependent helper function of CHCD4 contrasts with the recent description of other HVS-transformed CD4+ T cells that provide B cell help primarily via the membrane TNF-alpha and TNF-alphaR pathways. Furthermore, CHCD4 cells also secreted soluble factors that could mediate CD40-linked B cell differentiation into Ab-producing cells. Interestingly, this factor is not likely to be IL-2, IL-4, IL-6, IL-10, IL-15, TNF-alpha, or IFN-gamma as Abs against these cytokines were not able to inhibit the contact-independent B cell help by CHCD4. These results indicate that HVS-immortalization of CD4+ lymphocytes may produce T cell clones with a spectrum of important contact-dependent, as well as contact-independent, B cell helper function capacities.

B-Lymphocytes↗
PubMed1995

Human CD8+ T lymphocyte clones specific for T cell receptor V beta families expressed on autologous CD4+ T cells.

CD8+ T cells control immune responses, and recent studies suggest that this regulation is, in part, specifically directed towards TCR structures expressed by CD4+ cells. To develop a system to study the role of the TCR in regulatory interactions, we isolated clones of CD4+ cells expressing identified TCR V beta chains. These CD4+ clones were used to stimulate and expand autologous CD8+ cells, which kill the inducing CD4+ clone as well as independently isolated autologous CD4+ clones sharing the same TCR V beta as the inducing cell but not CD4+ T cells expressing different V beta TCRs. This V beta-specific cytotoxicity is dependent on the state of activation of the target cells and is not inhibited by an anti-class I monoclonal antibody, W6/32. We envision that V beta-specific CD8+ T cells of this type may regulate immune responses by direct interaction with antigen-activated CD4+ cells.

CD4-Positive T-Lymphocytes↗
PubMed1995

Murine CD8+ T cells that specifically delete autologous CD4+ T cells expressing V beta 8 TCR: a role of the Qa-1 molecule.

Interactions mediated by TCRs expressed on different T cell subsets may play a role in immunoregulation. To investigate this idea, we studied the regulation of superantigen-induced TCR V beta-restricted responses. We asked whether the in vivo regulation of CD4+ V beta 8+ T cells following SEB injection is controlled by CD8+ T cells. We found that in mice deficient in CD8+ T cells, the down-regulation of CD4+ V beta 8+ T cells below baseline is not observed. Moreover, following SEB administration, CD8+ T cells emerge that preferentially kill subpopulations of activated CD4+ V beta 8+ but not CD4+ V beta 8- T cells in vitro. This TCR V beta-specific cytotoxicity is dependent on beta 2-microglobulin and is inhibited by antisera specific for Qa-1 but not by antibody to MHC class Ia. These data suggest the idea that the specificity of immune regulation may involve CD8+ T cell recognition of TCR V beta determinants and Qa-1 molecules expressed on CD4+ T cells.

Animals↗
PubMed1995

Bone scanning in the multiply injured patient.

A prospective study was undertaken to evaluate the role of radionuclide bone scanning in the management of patients with multiple injuries. During a 7 month period, 14 patients with multiple injuries underwent a bone scan in order to identify occult skeletal injuries. All of the patients had new injuries diagnosed. The majority of new injuries occurred either in a limb in which an injury had already been diagnosed at presentation, or in the chest. Such findings are consistent with previously published data. Infrequently, there was a change in management of the patients in this series following the bone scan.

Adolescent↗
PubMed1994

Functional role of VLA-1 (CD49A) in adhesion, cation-dependent spreading, and activation of cultured human T lymphocytes.

The functions of VLA-1 (CD49a, alpha 1 beta 1 integrin), a potential ECM protein receptor on activated human T lymphocytes in vivo, were investigated. Within a panel of 25 long-term cultured IL-2-dependent T cell lines, tau delta and CD8+ alpha beta cells expressed significantly higher levels of alpha 1 beta 1 than CD4+ alpha beta cells. While VLA-1-high tau delta or CD8+ cells adhered to plastic wells coated with collagen IV, collagen I, or fibronectin, moAb 1B3.1 to VLA-1 only inhibited the adherence to collagen IV. tau delta and CD8+ VLA-1-high T cells layered upon collagen IV in the presence of Mg2+ also spread elongated cytoplasmic extensions, which were abrogated by moAb 1B3.1. In contrast, spreading on fibronectin or spontaneous non-ECM-related spreading were not inhibited. Crosslinking of surface VLA-1 molecules with plastic-bound moAb 1B3.1 selectively induced expression of IL-2R on two of six VLA-1+ clones, both of which expressed tau delta TCR. Thus, CD49a is a specific collagen IV receptor in VLA-1-high tau delta and CD8+ alpha beta cells and can transmit signals to these lymphocytes to spread and express IL-2R.

Antibodies, Monoclonal↗
PubMed1994

Isolation of cDNAs encoding T-BAM, a surface glycoprotein on CD4+ T cells mediating contact-dependent helper function for B cells: identity with the CD40-ligand.

"T-cell B-cell Activating Molecule" (T-BAM) is an activation-induced surface protein on CD4+ T cells that mediates a contact-dependent signal for B cell differentiation and immunoglobulin (Ig) secretion. The T-BAM protein on a helper clone of Jurkat (D1.1) was affinity purified using the anti-T-BAM mAb, 5c8. The NH2-terminal amino acid sequence of purified T-BAM was determined and found to be highly homologous to the predicted NH2-terminal sequence of a T cell ligand to the B cell CD40 molecule (CD40-L). From a D1.1 cDNA library, a clone was isolated that encodes CD40-L by sequence and drives expression of T-BAM protein on transfected cells, demonstrating that the T-BAM and CD40-L genes and proteins are identical. Moreover, transfection of T-BAM was shown to confer to non-lymphoid cells, the ability to induce B cells to upregulate the expression of surface CD23 molecules. In previous studies we showed that T-BAM was expressed predominantly on activated CD4+ and on few if any CD8+ cells. Although the current work confirms that T-BAM is largely restricted to activated CD4+ T cells, we now provide definitive evidence that T-BAM can be expressed by a small population of CD8+ T cells after activation. Importantly, a subset of CD8+ T cells do not express T-BAM after activation and this T-BAM- phenotype is maintained on certain CD8+ T cell clones. Taken together, these data unify the biology and structure of T-BAM and CD40-L and this synthesis has implications for understanding the T cell regulation of the humoral immune response.

Amino Acid Sequence↗
PubMed1991

Specific triggering of gamma, delta T cells by K562 activates the gamma, delta T cell receptor and may regulate natural killer-like function.

Freshly isolated and resting gamma/delta T cell lines, although capable of lysing a variety of MHC-unrestricted targets, fail to lyse K562. Yet, the killing of K562 can be specifically induced by antibodies to CD3 or delta-chains. Although this phenomenon may be caused by redirected lysis, it also raised the possibility that K562 may possess ligands capable of specifically interacting with the gamma/delta receptor. We found that K562 specifically induced both CD3 and delta modulation as well as IL-2R expression and IL-2 production by gamma/delta cells, supporting the idea that the TCR-gamma/delta is specifically triggered by K562 cells. Moreover, although the gamma/delta cell clones lysed other target cells (e.g., Molt 4, U937, Jurkat etc.), these latter targets did not induce delta modulation or IL-2R expression. In addition, F(ab)2 anti-CD3 antibodies inhibited activated gamma/delta T cells from killing K562 but did not inhibit the lysis of the other targets. Taken together, these results suggest that gamma/delta cells lyse some targets by utilizing receptors (perhaps NK-like) distinct from the gamma/delta receptor. We also found that triggering of the gamma/delta receptor by K562 inhibited the capacity of resting gamma/delta to lyse Molt 4 cells under conditions in which the K562 cells were not lysed. These findings suggest that the gamma/delta receptor maybe directly involved in the lysis of certain targets (i.e., K562) and, importantly, may potentially regulate the function of NK-like receptors that are involved in the lysis of other targets.

Animals↗
PubMed1991

Human gamma delta T cells amplify IgE production by Epstein-Barr virus-activated B cells.

In summary, these data document that gamma delta T cells regulate B cell differentiation, antibody synthesis, and IgE secretion in EBV-activated B cells. The classical "helper" subset of CD4+ alpha beta T cells, although potent inducers of other Ig isotypes, are not as efficient in augmenting IgE synthesis. However, interactions between alpha beta and gamma delta cells enhance the IgE response further. The precise mechanism by which gamma delta T cells function to augment IgE secretion is under study. It will be important, for example, to determine whether gamma delta T cells, or products of these cells, directly regulate class switching or mediate the clonal expansion of IgE-expressing B cells. In this regard, we ruled out the possibility that IL-4 release alone could replace gamma delta cells in increasing IgE secretion. Finally, we think it is of potential interest that gamma delta cells migrate to skin epithelia as well as gastrointestinal and pulmonary mucosa, sites of invasion by parasitic organisms and contact with allergens. If gamma delta T cells were specifically activated, either directly or indirectly, by these foreign pathogens, then the data presented here might elucidate the cellular basis for the events leading to IgE secretion, a critical step in the immune response to both parasites and allergens.

B-Lymphocytes↗