Trophoblastic disease monitoring.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to T J O'Brien.
Explore the source record for details and available documents.
The gene for superoxide dismutase-1 (SOD-1) is clearly on chromosome 21, although there is disagreement on the precise band location of SOD-1 on the long (q) arm of number 21. We report a patient with normal superoxide dismutase-1 (SOD-1) activity and an interstitial deletion of chromosome 21 resulting in monosomy for band q21. His phenotype is characterized by moderate mental retardation, a long narrow face, high and arched palate, cardiac murmur, undescended testes, and long hyperflexible extremities. The normal SOD-1 activity supports localization of this enzyme to 21q22.1.
Upon Isoelectric Focusing (IEF) of premenopausal uterine myometrial cytosol, specific binding of estradiol (E2) can be shown at elution pH's (EpH) of 4.0-4.4, 5.0-5.2, 5.8-6.2 and 7.5-8.0. Pre-adsorption of premenopausal uterine cytosol by Concanavalin A Sepharose (Con-A) or precipitation with 30% ammonium sulfate results in loss of estradiol binding at EpH's 4.4 and 5.0. The estradiol binding sites that bind to Con-A are present in plasma and have been shown to be Sex Hormone Binding Globulin (EpH = 5.0) and Estrogen Binding Protein (EpH = 4.4). After Con-A adsorption premenopausal cytosol preincubated with 2 nM 3HE2 reveals a single peak on IEF at EpH's congruent to 6.0, while preincubation with 40 nM 3HE2 reveals specific binding peaks at EpH's of congruent to 6.0 and 7.5-8.0. Postmenopausal uterine cytosol preincubated with either 2 or 40 nM 3H-E2 on IEF reveals EpH = 5.8-6.0 binding only. Post-labeling of IEF fractions with 20 nM 3HE2 demonstrates one peak at EpH 5.8-6.0 in postmenopausal tissue and two peaks (5.8-6.2 and 7.5-8.0) in premenopausal tissue. Scatchard analysis of postmenopausal cytosol demonstrates a single population of binding sites with a dissociation constant (Kd) of 10(-10) M. Premenopausal cytosol on Scatchard analysis contains two estradiol binding populations with Kd's of 10(-10) and 10(-9) M. The data suggest that the 10(-10) M E2 binding population has a EpH of 5.8-6.2, while the 10(-9) M component has an EpH of 7.5-8.0.
We analyzed the survival results of 300 consecutive kidney transplants (TXs) performed at Hennepin County Medical Center, Minneapolis, Minnesota, between March 1965 and April 1980. The graft survival result were compared between three sequential time periods, each comprising 100 renal TXs. The proportion of live donor TXs decreased from 27% in period 1 to 16% in period 2 and 5% in period 3, while the number of older patients, diabetic and multiple TX patients increased steadily. A comprehensive patient care scheme utilizing clinical protocols was developed in period 2 and carried out effectively in period 3. The Cox multivariate regression models used in this analysis allowed us to assess the influence of each variable on the graft survival results, while the effects of all others were held constant. Among the nondiabetic patients who received antilymphocyte globulin, the 1 and 5 year graft survival rates were 59.7 and 38.8% in period 1, 85.3 and 74.3% in period 2, 90.4 and 83.1% in period 3 (periods 1 versus 2: P = 0.008, periods 1 versus 3: P less than 0.0001). This improvement in graft survival was independent of the effects of the following variables, that is, the recipient's age, donor source, prior dialysis, co-existing medical problems, splenectomy, previous TXs, blood transfusions, cytotoxic antibodies, cold ischemia time, HLA mismatches, and post-TX acute tubular necrosis. Our observations indicate that reduced immunosuppression, frequent use of biopsy specimens and comprehensive patient care, played an important role in minimizing the loss of renal transplants in the later time periods and contributed indirectly for the improved graft survival results of our institution.
Explore the source record for details and available documents.
Renal hyperparathyroidism can be a major clinical problem in those receiving dialysis treatment and in those having renal transplants. This review of 66 patients during a five year period has led us to believe that laboratory data are useful for confirming the clinical diagnosis or for following the outcome of medical or surgical therapy. The screening for renal hyperparathyroidism should be on clinical grounds and not on isolated biochemical tests. All patients with renal failure, whether receiving dialysis therapy or renal transplantation, are at risk for having renal hyperparathyroidism develop. A careful assessment of the clinical and biochemical data is required to ensure proper patient selection for operation. Bone disease and persistent pruritus unresponsive to medical management remain the principle clinical indications for operation. Our preferred procedure is the standard subtotal parathyroidectomy.
Following the intravenous infusion of Solu-Medrol (methylprednisolone sodium succinate), anaphylactic shock developed in a 41 year old man on two consecutive occasions, six weeks apart. Intracutaneous testing with different components of he Solu-Medrol Mix-O-Vial demonstrated that the patient was allergic to methylprednisolone sodium succinate but not to other ingredients. In view of the recent increase in the popularity of steroid pulse therapy, we believe that all clinicians should be aware of this unusual and potentially fatal reaction to Solu-Medrol.
A method is described, and validated for hGH, using a double antibody immunoradiometric assay and a universal antibody coupled to a chelating moiety that can be labeled as the terminal step in the assay procedure. This technique, usable for any antigen, precludes the need for radiolabeled specific antibodies, and because of the short-lived radionuclide used in the terminal labeling step, generates no radioactive waste. The assay itself uses a specific first antibody coupled to a solid support (paper disc) to which the antigen binds. A specific second antibody from a second species is then attached to the solid phase retained antigen. Now a third antibody is attached, which has been generated from a third species against the second antibody acting as an antigen, and which carries transferrin as a chelating moiety. This final complex is labeled with 113mIn and the plot of the percentage of the total activity bound against the hGH concentration provides the derived values for the antigen levels present in the assay solution.
A 3 1/2-year-old female with clinical features of Down's syndrome was found to have extra chromosome material on the long arm of one of the X chromosomes, 46,XXq+. The parental karyotypes were normal. In the light of the clinical features of the proband an the banding characteristics of the extra chromosome material, the patient was thought to have a de novo (X;21) translocation. The results of late replication studies with BUdR and enzyme superoxide dismutase (SOD) assays in the proband suggest that: (1) the presumed (X;21) translocation chromosome was the late replicating chromosome; (2) the spread of inactivation extended from the Xq segment of the translocation chromosome to the proximal part of the segment derived from chromosome 21, leading to the inactivation of the autosomal gene for enzyme SOD; (3) the remaining distal portion of the (X;21) translocation chromosome, a part of a segment presumably derived from chromosome 21, was spared from the spread of inactivation so that this part was still genetically active and responsible for the Down's phenotype; (4) therefore, the main determinants for a Down's phenotype may be located more distally (q22.2 or q22.3 or both) than the SOD gene (q22.1) on the long arm of chromosome 21.
A plasma/serum estrogen-binding protein (E2BP) which is distinct from testosterone-estradiol-binding globulin (TEBG) has been documented. This high affinity, low capacity estrogen binder is readily detectable in the mannoglycoprotein fraction of serum or plasma. It can be distinguished from TEBG by 1) its isoelectric elution pH (pH 3.9 as distinct from pH 4.9 for TEBG); 2) its sedimentation value on sucrose gradients (a lower sedimentation value compared to TEBG); and 3) its steroid specificity (a high affinity for diethylstilbestrol with essentially no affinity for dihydrotestosterone or testosterone, in contrast to TEBG which has no affinity for diethylstilbestrol and a high affinity for dihydrotestosterone and testosterone).
Explore the source record for details and available documents.
Protein maps of in vitro hormone-modulated adenocarcinoma cells from an endometrial tumor are described. It is noted that mapping of tumor tissues by means of the two-dimensional analysis described by O'Farrell and associates of 35S-methionine-labeled proteins can provide a characteristic map for each tumor and that the methionine-containing proteins of tumor cells can be independently modulated by the in vitro additions of estradiol and progesterone. Such protein modulation could be indicative of hormonal therapeutic responsiveness of individual endometrial adenocarcinomas and other hormone receptor-positive tumors. Tumor maps may further provide data for the identification and isolation of new tumor markers which might be correlated with the radiotherapeutic and chemotherapeutic sensitivity of the malignancy.
Extracts of hydatidiform mole vesicles and the fluid contained in these vesicles were shown to contain a trophoblastic androgen binding protein. This protein was found to be distinct from serum testosterone-estradiol binding globulin (TEBG) by its isoelectric point, its affinity for dihydrotestosterone (DHT) and by Concanavalin A binding. The elution pH of this binding protein was shown to be 4.6, whereas that of TEBG was pH 5.2-5.3. The apparent dissociation constant (Kd app) for TEBG as determined by Scatchard analysis was 2.0 X 10(-9) M, whereas the Kd app for the trophoblastic binding protein after isoelectric focusing was 1.5 X 10(-10) M. A second binding protein found in both vesicular extracts and mole fluid was shown to have an isoelectric elution value (pH 5.2) similar to TEBG and an Kd app of 1.7 X 10(-9) M DHT, very close to the TEBG value. Apparent equilibration for both proteins with DHT was shown to occur in approximately 4H, and both proteins were shown to be high affinity, low capacity binders. The relative affinities of both proteins for other steroids was found to be similar except for methyltrienolone, which appeared to have a higher affinity for the trophoblastic binding protein.
Explore the source record for details and available documents.
Pregnancy-specific beta 1-glycoprotein (SP1) was evaluated as a potential marker protein for monitoring trophoblastic disease. Four patients with post-molar pregnancy accompanied by spontaneous titer remission and three patients with nonmetastatic trophoblastic disease were found to have regression curves for both human chorionic gonadotropin (hCG) and SP, which closely followed each other. Of three patients with metastatic choriocarcinoma, two were shown to have discordant hCG and SP1 patterns, SP1 in both cases was plateauing or rising while hCG continued to fall. Two other patients are described, one with a spontaneous remission, and one who previously had had choriocarcinoma and was found to have low levels of hCG with higher levels of SP1.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.