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Biomedical subjects

A Chai

Publications and source records attributed to A Chai.

14 recordsLinked to original sources
PubMed1997

Discovery and analysis of inflammatory disease-related genes using cDNA microarrays.

cDNA microarray technology is used to profile complex diseases and discover novel disease-related genes. In inflammatory disease such as rheumatoid arthritis, expression patterns of diverse cell types contribute to the pathology. We have monitored gene expression in this disease state with a microarray of selected human genes of probable significance in inflammation as well as with genes expressed in peripheral human blood cells. Messenger RNA from cultured macrophages, chondrocyte cell lines, primary chondrocytes, and synoviocytes provided expression profiles for the selected cytokines, chemokines, DNA binding proteins, and matrix-degrading metalloproteinases. Comparisons between tissue samples of rheumatoid arthritis and inflammatory bowel disease verified the involvement of many genes and revealed novel participation of the cytokine interleukin 3, chemokine Gro alpha and the metalloproteinase matrix metallo-elastase in both diseases. From the peripheral blood library, tissue inhibitor of metalloproteinase 1, ferritin light chain, and manganese superoxide dismutase genes were identified as expressed differentially in rheumatoid arthritis compared with inflammatory bowel disease. These results successfully demonstrate the use of the cDNA microarray system as a general approach for dissecting human diseases.

Arthritis, Rheumatoid↗
PubMed1997

Pharmacokinetic modeling and absorbed dose estimation for chimeric anti-CEA antibody in humans.

UNLABELLED: The objective of this article was to model pharmacokinetic data from clinical diagnostic studies involving the 111In-labeled monoclonal antibody (MAb) chimeric T84.66, against carcinoembryonic antigen. Model-derived results based on the 111In-MAb blood, urine and digital imaging data were used to predict 90Y-MAb absorbed radiation doses and to guide treatment planning for future therapy trials. Fifteen patients with at least one carcinoembryonic antigen-positive lesion were evaluated. We report the kinetic parameter estimates and absorbed 111In-MAb dose and projected 90Y-MAb doses for each patient as well as describe our approach and rationale for modeling an extensive set of pharmacokinetic data. METHODS: The ADAPT II software package was used to create three- and five-compartment models of uptake against time in the patient population. The "best-fit" model was identified using ordinary least squares. Areas under the curve were calculated using the modeled curves and input into MIRDOSE3 to estimate absorbed radiation doses for each patient. RESULTS: A five-compartment model best described the liver, whole body, blood and urine data for a subcohort of nine patients with digital imaging data. A three-compartment model best described the blood and urine data for all 15 clinical patients accrued in the clinical trial. For the subcohort, the largest projected 90Y-MAb doses were delivered to the liver (mean, 24.78 rad/mCi; range, 15.02-37.07 rad/mCi), with red marrow estimates on the order of 3.32 rad/mCi (range, 1.24-5.55) of 90Y. Corresponding estimates for the 111In-MAb were 3.18 (range, 2.09-4.43) and 0.55 (range, 0.34-0.74), respectively. CONCLUSION: The three- and five-compartment models presented here were successfully used to represent the blood, urine and imaging data. This was evidenced by the small standard errors for the kinetic parameter estimates and R2 values close to 1. As planned future therapeutic trials will involve stem cell support to alleviate hematological toxicities, the development of an approach for estimating doses to other major organs is crucial.

Adult↗
PubMed1996

Parallel human genome analysis: microarray-based expression monitoring of 1000 genes.

Microarrays containing 1046 human cDNAs of unknown sequence were printed on glass with high-speed robotics. These 1.0-cm2 DNA "chips" were used to quantitatively monitor differential expression of the cognate human genes using a highly sensitive two-color hybridization assay. Array elements that displayed differential expression patterns under given experimental conditions were characterized by sequencing. The identification of known and novel heat shock and phorbol ester-regulated genes in human T cells demonstrates the sensitivity of the assay. Parallel gene analysis with microarrays provides a rapid and efficient method for large-scale human gene discovery.

Cells, Cultured↗
PubMed1996

Histopathologic effects of tamoxifen on the uterine epithelium of breast cancer patients: analysis by menopausal status.

We evaluated the histopathologic changes of the uterine epithelium in 73 breast cancer patients with tamoxifen stratified by menopausal status. Clinicopathologic data at the time of breast cancer diagnosis and endometrial sampling were analyzed and compared with 122 breast cancer patients not receiving the drug. The incidence of endocervical and/or endometrial polyps was increased in tamoxifen-treated postmenopausal patients compared with untreated patients, 43% (25 of 58) and 24% (16 of 68), respectively (odds ratio=2.46, P=0.02). In contrast, there was no increase in polyps in premenopausal tamoxifen-treated patients. This finding suggests that the effects of tamoxifen on the endometrium may vary with menopausal status.

Adenocarcinoma↗
PubMed1996

In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission.

PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.

Adolescent↗
PubMed1995

On the correction for radioactive decay in pharmacokinetic modeling.

The question of how to include radioactive decay during biological modeling with first-order differential equations was considered. Modeling may involve either experimental data y(t) or decay-corrected data z(t) [identical to exp(lambda t)y(t) where lambda is the decay constant] for each compartment. It is sometimes assumed that the latter are solutions to corresponding purely pharmacokinetic models (no decay). We primarily compared the two analyses in the case where the model did not require simultaneous consideration of both labeled and unlabeled material. A general theorem was found which limits the use of decay-corrected data to pharmacokinetic models containing linear, homogeneous differential equations. By way of verification, an example of this model type was analyzed for a chimeric monoclonal antibody biodistribution in man. Even in this case, statistically significant differences between the two solutions showed that one may find different model parameters depending upon which data set (y or z) was analyzed. For other mathematical forms, the analyst must include the physical decay in all relevant compartments. By analyzing an open, quadratic model, effects of not including decay were seen to be maximized if the biological rate constant was > or = lambda, the physical decay constant. Finally, using monoclonal antibody-antigen reactions, similar discrepancies between the z functions and the pharmacokinetic variables were demonstrated. This result was found to persist even if competitive molecules were included. We conclude that decay-corrected data may be shown, but should not be entered into the modeling equations unless the latter are of the linear, homogeneous form.

Antibodies, Monoclonal↗
PubMed1994

Effect of H-2 compatibility in autoimmune destruction of islet allografts from B10 congenic lines to nonobese diabetic mice.

Autoimmune diabetes involves multiple antigens, and both cellular and humoral immune responses. Using CBA (H-2k) C57BL/6 (H-2b), and BALB/c (H-2d) newborn mouse pancreata, we previously demonstrated that acute and strong destruction of islet allografts by anti-islet autoimmunity in the nonobese diabetic (NOD) mouse H-2Kd, Db) is under the influence of major histocompatibility complex (MHC) antigens. In the current study, we have attempted to confirm these results in the absence of minor alloantigenic differences using B10 congenic strains as pancreatic donors. Pancreata from B10.BR (H-2k), C57BL/10SnJ (H-2b), and B10.D2 (H-2d) were transplanted under the kidney capsule of NOD mice within 1 month of diabetes onset. These recipients were immunosuppressed with cyclosporine (CsA) in a dosage that effectively prevents rejection of skin allograft, but not islet isograft destruction that is mediated by anti-islet autoimmunity. On day 10, the grafts were harvested and examined histologically to assess viability. Pancreatic allografts from B10.D2, sharing the H-2Kd with the NOD mouse, showed the strongest lymphocytic infiltration, and neither islets nor beta cells were found in all seven grafts. C57BL/10SnJ grafts, sharing the same H-2Db, also showed severe lymphocytic infiltration, and no intact islets, and only a few beta cells were found, as single cells, in three of eight grafts. In contrast, B10.BR grafts, completely incompatible at the H-2, showed the least infiltration, and normal islets containing many beta cells were found in 10 of 11 grafts. These results again suggested the hypothesis that islet allograft destruction by diabetic NOD mice is MHC restricted.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Prevention of diabetes in nonobese diabetic mice by dendritic cell transfer.

The purpose of this study was to determine the effect of dendritic cell (DC) transfers on the incidence of diabetes in female nonobese diabetic (NOD) mice. Groups of 4-wk-old NOD female mice were given a single foot pad of DCs (70-90% purity) isolated from the draining lymph nodes (LN) of the pancreas (PLN), the cervical LNs, or the axillary/inguinal LNs. In addition, other groups of NOD mice received purified spleen DCs, purified PLN T cells (the major contaminating population in DC preparations), or the injection vehicle PBS. All groups were monitored for diabetes for one year. Significant protection from diabetes was observed in NOD mice receiving greater than 1 x 10(4) PLN DCs in comparison to mice receiving other DCs populations, PLN T cells, or PBS (P less than 0.05). The pancreata of NOD mice that received PLN DCs demonstrated significantly lower levels of lymphocytic infiltration in the islets that age-sex matched nondiabetic female NOD control mice (P less than 0.05). LN cells from nondiabetic NOD mice that received PLN DC protected irradiated female recipients from the adoptive transfer of diabetes to a greater degree than LN cells from age and sex matched nondiabetic female NOD mice that did not receive PLN DC transfers at 36 d (P = 0.014) and at 1 yr (P = 0.0015) after transfer. These data suggest that the PLN DC transfers are able to modulate autoimmunity and limit diabetes expression in the NOD mouse. PLN DCs transfers may regulate autoimmunity by the induction of regulatory cells.

Animals↗
PubMed1989

Identification of growth hormone at the myocardial cell surface.

Growth hormone immunoreactivity has been demonstrated in a variety of normal human tissues, and ectopic production has been documented in a number of malignant tumors. However, myocardium has not previously been reported to contain growth hormone. Monkey anti-rat growth hormone antiserum was used in a sensitive immunoperoxidase staining method to histologically localize growth hormone in myocardium obtained from normal rats and rats harboring growth hormone-secreting tumors. Immunoreactive growth hormone was localized to the myocardial cell surface and was not seen in vascular endothelial cells of small arteries, veins, or capillaries. No intracellular staining of myocytes was evident. Specific staining was abolished by neutralization with purified growth hormone. Specific staining was abolished by neutralization with purified growth hormone. Myocardial cells did not stain with anti-triiodothyronine or anti-thyroxine immune serum. The cell surface staining is consistent with the binding of growth hormone to the myocardial cell surface, as it is unlikely that the myocardium synthesizes growth hormone polypeptide. These findings suggest that growth hormone may have a direct growth promoting or metabolic effect on cardiac tissue.

Animals↗
PubMed1988

Expression of genetically determined diabetes and insulitis in the nonobese diabetic (NOD) mouse at the level of bone marrow-derived cells. Transfer of diabetes and insulitis to nondiabetic (NOD X B10) F1 mice with bone marrow cells from NOD mice.

The development of autoimmune diabetes in the nonobese diabetic (NOD) mouse is controlled by at least three recessive loci, including one linked to the MHC. To determine whether any of these genetic loci exert their effects via the immune system, radiation bone marrow chimeras were constructed in which (NOD X B10)F1-irradiated recipients were reconstituted with NOD bone marrow cells. Unmanipulated (NOD X B10)F1 mice, or irradiated F1 mice reconstituted with F1 or B10 bone marrow, did not display insulitis or diabetes. In contrast, insulitis was observed in a majority of the NOD----F1 chimeras and diabetes developed in 21% of the mice. These data demonstrate that expression of the diabetic phenotype in the NOD mouse is dependent on NOD-derived hematopoietic stem cells. Diabetogenic genes in the NOD mouse do not appear to function at the level of the insulin-producing beta cells since NOD----F1 chimeras not only developed insulitis and diabetes but also rejected beta cells within pancreas transplants from newborn B10 mice. These data suggest that the beta cells of the NOD mouse do not express a unique antigenic determinant that is the target of the autoimmune response.

Animals↗
PubMedDate not supplied

Boundary detection of retinoblastoma tumors with neural networks.

Consistent and accurate measurement of retinoblastoma tumors is of important clinical value for treatment management. This paper presents an algorithm for the determination of retinoblastoma (RB) tumor to assist in the determination of tumor volume changes throughout treatment periods. The result of the development of a neural network approach for the analysis of three-dimensional ultrasound images shows that it is possible to identify retinoblastoma tumors and accurately determine the front and back boundary of the tumor. The algorithm used was a soft competitive learning network with two inputs. The outputs of the network identify the eye, the tumor, and the back of the eye.

Algorithms↗