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Biomedical subjects

S Stevens

Publications and source records attributed to S Stevens.

At least 19 recordsLinked to original sources
PubMed1992

Immunologic memory to phosphocholine keyhole limpet hemocyanin. Recurrent mutations in the lambda 1 light chain increase affinity for antigen.

Anti-phosphocholine (PC)-keyhole limpet hemacyanin hybridomas representative of a memory response that express the lambda 1 L chain isotype have a high reactivity to PC-protein. A common feature of these hybridomas possessing high affinity for PC-protein is the occurrence of somatic mutations resulting in replacement changes in three CDR2 positions of the lambda 1 L chain. The influence of each of these three positions on the Ag binding properties of these antibodies was examined by site-specific mutagenesis and expression of recombinant antibody molecules by transfected cells. Affinity measurements and fine specificity profile determinations demonstrated the importance of the three lambda 1 CDR2 positions in Ag binding. Compared to antibodies expressing germline lambda 1, including one with an additional junctional serine that is not encoded by V or J, those antibodies possessing critical changes in CDR2 would have a strong selective advantage based on affinity differences for Ag. Sequence analysis of a group of clonally related hybridomas expressing mutated lambda 1 genes allowed construction of a hypothetical genealogic tree that suggests selection based on changes in CDR2 of lambda 1 in the absence of H chain mutations. The results are consistent with stepwise acquisition of mutations and selection based on affinity constraints.

Animals↗
PubMed1992

Congenital anomalies of the inferior vena cava: embryogenesis and MR features.

This article describes the MR appearances of the six most common congenital anomalies of the inferior vena cava. As a basis for understanding those anomalies, it describes the embryology of the inferior vena cava, based on an actual study of embryos and fetuses. The article takes a fresh look at the original research in this area, discusses the possible embryogenesis of the relevant anomalies, and describes different opinions on that subject, where different opinions exist.

Congenital Abnormalities↗
PubMed1992

Human antibody response to the intravenous and intraperitoneal administration of the F(ab')2 fragment of the OC125 murine monoclonal antibody.

We have characterized the human immune response against murine monoclonal antibodies (HAMA) in 18 patients following administration of the F(ab')2 fragment of the murine monoclonal antibody OC125. OC125 is directed against the CA125 antigen, present on the surface of many human ovarian cancers. An affinity matrix was used to separate serum into immunoglobulin-containing and immunoglobulin-free fractions. HAMA titer was determined on the immunoglobulin fraction with an OC125 sandwich enzyme-linked immunosorbent assay (ELISA). All patients developed an HAMA response, despite the use of F(ab')2 fragments and small amounts (1-4 mg) of antibody. It may be that the intraperitoneal (i.p.) route provides a more marked HAMA response. Enzyme-linked sandwich immunoassays were also used to determine anti-isotype and anti-idiotype titers. Anti-isotype titers were analyzed with antigen irrelevant, isotype-matched murine antibodies and OC125-HRPO. Anti-idiotypes titers were assessed in a sandwich assay that utilized F(ab')2 and F(ab') fragments of OC125. The anti-isotype response tended to be of low titer and short duration, while the anti-idiotype response was of high titer and remarkably persistent. HAMA interfered in an unpredictable manner with the correct measurement of serum levels of CA125 in an enzyme immunoassay using OC125. Corrected values of CA125 could be obtained by measurement of antigen in the immunoglobulin-free fraction of serum. The response of one patient, who developed a markedly elevated anti-idiotype titer after serial i.v./i.p. injections, was further characterized and found to contain an antibody consistent with an anti-anti-idiotype to the CA125 antigen.

Adenocarcinoma↗
PubMed1992

Kinetics of technetium-99m-Sestamibi and thallium-201 in a transient ischemic myocardium animal model: insight into the 'redistribution' phenomenon.

This study was designed to determine the redistribution potential for technetium-99m (99mTc)-hexakis-2-methoxy isobutyl isonitrile (99mTc-Sestamibi) as compared to thallium-201 (201Tl) in a transiently ischemic swine heart model. The left anterior descending coronary artery (LAD) was totally occluded for 10 min. One minute prior to the release of the LAD, 99mTc-Sestamibi, 201Tl and a set of 95Nb-radiolabeled microspheres (15 microns) were injected. A second set of 51Cr-radiolabeled microspheres was injected prior to sacrifice in order to document reflow. Animals were sacrificed at different times post-LAD release (ranging from 1 min to 4 h). The left ventricle was sectioned into 0.2- to 0.5-gram pieces for the gamma spectroscopic counting of the 99mTc-Sestamibi, 201Tl and radiolabeled microspheres. Linear regression analysis of radiotracer localization versus microsphere-determined regional myocardial blood flow (rMBF) demonstrates an initial slight filling in of 99mTc-Sestamibi into transiently ischemic zones, with subsequent stable kinetics up to 4 h (i.e., it does not further redistribute). In comparison, the ischemic to normal ratios for 201Tl activity increase progressively in a time-dependent manner. These differences between 99mTc-Sestamibi and 201Tl might be explained on the basis of their blood clearance kinetics and/or their net clearance from normal and ischemic zones of the heart. It is concluded that 99mTc-Sestamibi is a stable and reliable indicator for rMBF over time, and that the lack of normalization of 99mTc-Sestamibi into transient ischemic zones will necessitate two separate injections for differentiation between ischemia and persistent defects.

Animals↗
PubMed1991

High-dose, short-duration cisplatin/doxorubicin combination chemotherapy for advanced ovarian epithelial cancer.

Sixty-one patients with epithelial ovarian cancer were treated with intensive high-dose, short-course chemotherapy that consisted of cisplatin (120 mg/m2) and doxorubicin (70 mg/m2) every 3 weeks for four cycles. Patients in complete clinical remission were offered second-look laparotomy (SLL). Patients with minimal or no residual disease at SLL were randomized to either cyclophosphamide (1000 mg/m2 every 21 days for six cycles) or whole-abdominal radiation therapy. All patients completed therapy with a median leukocyte nadir 1.3/microliter and platelet nadir of 90/microliters. Forty-five patients (74%) had a complete clinical response. Results of twenty-two of 36 second-look procedures (64%) showed no evidence of disease (NED). After SLL, 19 patients received six courses of cyclophosphamide and 16 patients received whole-abdominal radiation. Nine patient who refused SLL and one patient with negative SLL findings refused additional treatment. The median survival time for all patients was 51.3 months. High-dose intensive chemotherapy regimens have high response rates, but survival needs to be compared with traditional low-dose regimens. Although high-dose cisplatin and doxorubicin were myelosuppressive, the resulting complications were manageable. There was no significant difference between the mean survival times of patients receiving Cytoxan, abdominal radiation, or no treatment as second-line therapy.

Adult↗
PubMed1991

Initial clinical study of indium-111-labeled clone 110 anticarcinoembryonic antigen antibody in patients with colorectal cancer.

A murine monoclonal antibody directed against carcinoembryonic antigen (CEA) was labeled with indium-111 (111In) by means of a benzylisothiocyanate derivative of diethylenetriamine penta-acetic acid (DTPA) and used for clinical radioimmunodetection studies. Twenty-one patients having a history of surgically resected colorectal cancer and rising serum CEA levels suggestive of tumor recurrence were studied. Patients were infused over 20 minutes with 5, 10, or 20 mg of the monoclonal antibody labeled with 5 mCi of 111In. The mean radiochemical purity was greater than 96%. No toxicity was seen. The stability of the radiolabel on antibody in patient serum was demonstrated by high-performance liquid chromatography (HPLC), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with autoradiography, and immunoprecipitation for up to 96 hours after infusion. Tumor sites were identified in 20 of 21 patients. Sites of antibody accumulation in 20 patients were confirmed as tumor either by resection at laparotomy (16 patients) or fine-needle biopsy (four patients). Nine patients who had the identified lesion resected or irradiated showed return of the serum CEA antigen level to normal or near normal values. In the absence of high levels of circulating CEA (greater than 500 ng/mL), the disappearance of radioactivity from patient serum demonstrated first order elimination kinetics, with a mean half-life of 38 hours. The serum half-life was not affected by the dose of antibody administered or by serum CEA titers below 500 ng/mL. Despite a mean liver uptake of 18% injected dose (ID) 24 hours after administration, hepatic metastases were easily visualized as areas of increased uptake of radioactivity. Radioimmunodetection of recurrent colorectal cancer, not detected by computed tomographic (CT) scans, appears achievable with this agent. This may allow successful clinical intervention in selected patients.

Adult↗
PubMed1990

Pharmacokinetics in patients of an anti-carcinoembryonic antigen antibody radiolabeled with indium-111 using a novel diethylenetriamine pentaacetic acid chelator.

The pharmacokinetics of the C110 anti-carcinoembryonic antigen antibody radiolabeled with 111In via a novel benzylisothiocyanate derivative of diethylenetriamine pentaacetic acid have been determined in 12 patients. The chelator was attached to the protein via a thiourea bond and in such a way that all 5 carboxymethyl arms were presumably able to participate in chelation. Patients with known or suspected colorectal carcinoma received between 5 and 20 mg of the IgG antibody labeled with 5 mCi of 111In. Individual organ radioactivity levels were quantitated, and serum and urine samples were analyzed, principally by size exclusion high-performance liquid chromatography (HPLC). Total urinary excretion averaged 0.18% of the injected dose/h with large patient to patient variation. At early times postadministration (less than 8 h) the predominant radiolabeled species in urine was free diethylenetriamine pentaacetic acid most probably administered as a small radiocontaminant in the injectate. Thereafter, radioactivity in urine was primarily present as a low molecular weight catabolic product. Analysis of serum by size exclusion HPLC occasionally showed 3 radioactivity peaks, 2 of which are due to circulating immune complexes and labeled antibody. The third peak is of low molecular weight and is due to one or more products of antibody catabolism. Transchelation of 111In to circulating transferrin was observed but at modest levels. Quantitation of organ radioactivity showed that 18 +/- 4 (SD)% of the injected dose was in the liver at 1 day postadministration and 1.4 +/- 1.1 and 1.2 +/- 0.9% was in the spleen and in both kidneys, respectively, at this time. The mean half-life for clearance of total injected radioactivity was fitted to a single exponential and was found to be 34 h (SD, 14 h; N = 13) and that for antibody alone, assessed by size exclusion HPLC analysis of serum samples, was calculated to be 22 h (SD, 8 h; N = 10). Neither of these values nor organ radioactivity levels were affected by antibody-loading dose.

Adult↗
PubMed1989

Tissue- and species-specific expression of inhibitory guanine nucleotide-binding proteins. Cloning of a full-length complementary DNA from canine heart.

Three different isoforms of the inhibitory guanine nucleotide-binding protein alpha-subunit (Gi alpha) have been cloned. However, little information on the cardiac-specific expression of these isoforms is available. The deduced amino acid sequence of a full-length Gi alpha 2 complementary DNA from a canine ventricular library displays several unique residues compared with those from other species. In contrast to previously described complementary DNA clones for Gi alpha 2, this complementary DNA has a complete 3'-untranslated region with the expected consensus sequence for polyadenylation. Gi alpha 2 is the predominant isoform in the heart, and its message level of 14.7 +/- 4.9 pg/10 micrograms total ventricular RNA is about fourfold lower than that of the stimulatory guanine nucleotide-binding protein.

Amino Acid Sequence↗
PubMed1989

Women residents: expanding their role to increase treatment effectiveness in substance abuse programs.

It has long been noted that chemically dependent women have special needs that differ from the needs of chemically dependent men. A therapeutic community model, which has been found effective, suggests several changes in traditional treatment approaches. After intervention with our female-based therapeutic model, several positive changes occurred. Extremely disproportionate populations of males and females began to even out, with female residents' length of stay increasing dramatically. Length of stay for male residents also increased by a significant amount. Success of treatment, as measured by the number of drug-free ex-residents, also increased significantly for male and female populations.

Adult↗
PubMed1989

Children's solution strategies and mental rotation: evidence for a developmental shift.

We examined children's ability to anticipate the appearance of transformed multicomponents using visual stimuli with variations of a mental rotation task. We hypothesized that (a) performance would depend on the presence, location, and spatial relationship of specific stimulus features, and that (b) younger children would use a single component to make their predictions, whereas older children would be more likely to use multiple components. In Study 1, 40 first-, and fifth-grade subjects were presented with 32 rotation problems consisting of varied stimulus characteristics; subjects selected the correct option from a field where foils were indicative of the strategy used. Analyses of variance and log linear analyses revealed the hypothesized stimulus effect differentially associated with the children's ages. In Study 2, sixty 5-, 7-, and 9-year olds confronted 64 mental rotation problems with multicomponent stimuli and a construction task. Results and implications confirmed those of Study 1.

Attention↗
PubMed1988

Radiation-induced increases in sensitivity of cataleptic behavior to haloperidol: possible involvement of prostaglandins.

The effects of radiation exposure on haloperidol-induced catalepsy were examined in order to determine whether elevated prostaglandins, through an action on dopaminergic autoreceptors, could be involved in the radiation-induced increase in the potency of this neuroleptic. Cataleptic behavior was examined in animals irradiated with various doses of gamma photons (1-150 Gy) and pretreated with a subthreshold dose of haloperidol (0.1 mg/kg). This approach was chosen to maximize any synergistic effects of radiation and haloperidol. After irradiation with doses less than or equal to 30 Gy, the combined treatment of haloperidol and radiation produced catalepsy, whereas neither treatment alone had an effect. This observed catalepsy could be blocked with prior administration of indomethacin, a prostaglandin synthesis inhibitor. Animals exposed to doses of radiation less than or equal to 50 Gy and no haloperidol, however, displayed apparent catalepsy. This effect was also antagonized by indomethacin. Prostaglandins can induce catalepsy and when administered in subthreshold doses along with subthreshold doses of haloperidol, catalepsy was observed. In order to assess a possible action of prostaglandins and radiation on dopaminergic activity, the functioning of striatal dopaminergic autoreceptors was examined by determining the effects of varying concentrations of haloperidol on the K+-evoked release of dopamine from striatal slices obtained from parallel groups of animals treated as above. Results indicated that sensitivity to haloperidol increased (higher K+-evoked dopamine release) in slices from irradiated or prostaglandin-treated animals and that this increase in sensitivity was blocked by indomethacin. Results from both experiments suggest that radiation-induced increases in endogenous neuronal mediators, such as prostaglandins, can induce catalepsy through an action on dopaminergic autoreceptors.

Animals↗
PubMed1979

The response of ataxia telangiectasia cells to bleomycin.

The autosomal recessive disorder, ataxia telangiectasia (AT) is characterised by cellular sensitivity to ionizing radiation. The molecular basis of this radiosensitivity is the subject of controversy. We report here that cultured fibroblasts from AT patients are also sensitive to the lethal effects of bleomycin. As with ionizing radiation, no defect has been observed in the overall rejoining of single or double-strand breaks produced by bleomycin. Since, however, only apyrimidinic (and to a lesser extent apurinic) sites and strand breaks are known to be produced by bleomycin, we tentatively suggest that AT cells are unable to rejoin a very small fraction of the total strand breaks. We attribute our inability to detect such unrejoined strand breaks to the relative insensitivity of the sucrose gradient procedures normally used to detect strand breaks.

Ataxia Telangiectasia↗
PubMed1977

The production and repair of double strand breaks in cells from normal humans and from patients with ataxia telangiectasia.

The production and repair of double strand breaks induced by gamma-rays in the DNA of human fibroblasts have been measured by sedimentation in sucrose radients under non-denaturing conditions. Unirradiated DNA formed a rapidly sedimenting gel. Low doses of radiation released freely sedimenting DNA molecules from this gel. Higher doses reduced the rate of sedimentation of the free DNA due to the introduction of double strand breaks. The breakage efficiency was 1 break/1.3 X 10(10) daltons of DNA/krad. Postirradiation incubation after a high dose of radiation resulted in an increase in molecular weight of the free DNA molecules, and after a low dose the rapidly-sedimenting gel was reformed. The data suggest that double strand breaks are repaired in human fibroblasts. No significant differences were found between fibroblasts from two normal donors and four patients with the radiosensitive disorder, ataxia telangiectasia, in either the production or repair of double strand breaks.

Ataxia Telangiectasia↗