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Biomedical subjects

D M Adams

Publications and source records attributed to D M Adams.

At least 37 records · Page 2Linked to original sources

Understanding prostaglandin metabolites and platelet-activating factor in the pathophysiology and treatment of the antiphospholipid syndrome.

As clinicians include an immunologic evaluation in their assessment of recurrent fetal loss among otherwise asymptomatic women, the diagnosis of PAPS will be uncovered with greater frequency. Our understanding of the underlying pathophysiology of PAPS is critical if we are to propose safe and rational therapies for these patients. It appears as though prostaglandin metabolites are implicated directly in the processes that culminate in this unique, localized vasculopathy; and research is actively progressing with this focus in mind. For the present, we should look critically at the available treatments to be sure that the rationale for use is consistent with current evidence and that the margin of fetal and maternal safety justifies their use. To date, only low-dose aspirin appears to alter prostaglandin metabolites favorably and is thus, emerging as our safest and most efficacious treatment.

Abortion, Habitual↗

Accurate intrapartum estimation of fetal platelet count by fetal scalp samples smear.

Fetal scalp sampling has been used to determine fetal platelet count in early labor. Because platelet clumping may lead to falsely low platelet counts, this pilot study was carried out to evaluate an improved method of scanning an intrapartum fetal scalp smear for platelet estimation. We report 5 years' experience with the use of scanning of the smear for platelet aggregates instead of direct measurement of platelets. In 22 cases, intrapartum examination of the scalp blood smear at low power revealed the great majority of high-power, dry microscopic fields devoid of platelets, whereas isolated fields contained aggregates of more than 10 platelets. In one case, an adequate number of platelets were evenly distributed. Intrapartum fetal platelet estimation by scanning of the smear (using these platelet aggregates) correctly identified an adequate neonatal platelet count in 23 cases (mean, 264,600 +/- 15,000; range, 133,000 to 396,000). Cesarean section was avoided in 82.6% of these cases. In this pilot study, platelet estimation on fetal scalp sample were reliably performed by scanning of the smear for platelet aggregates. When aggregates were seen, platelet adequacy was found in all cases.

Blood Specimen Collection↗

Perceived family functioning and adolescent suicidal behavior.

OBJECTIVE: Family problems increase the risk of adolescent suicidal behavior, but the specific dimensions of family functioning related to adolescent suicidal ideation and suicide attempts have not been identified clearly. This study examined the relationship between family functioning and adolescent suicidal ideation and suicide attempts. Participating adolescents included psychiatric inpatients who had attempted suicide (n = 35), high school students reporting suicidal ideation (n = 33), nonsuicidal psychiatric inpatients (n = 29), and nonsuicidal high school students (n = 37). METHOD: The Family Assessment Measure was used to assess adolescents' perceptions of family functioning on two levels: (1) the family system and (2) parent-adolescent dyadic relationships. RESULTS: The suicidal psychiatric inpatients and the suicidal high school students did not differ in their perceptions of family functioning and mother-adolescent relationships. However, both suicide groups reported more distress and family dysfunction than did the nonsuicidal high school students. Perceived family functioning and mother-adolescent relationships were significantly correlated with levels of depression, hopelessness, and self-esteem. CONCLUSIONS: Family functioning is important to consider when assessing and treating adolescents for suicidal behavior.

Adolescent↗

Stressful life events associated with adolescent suicide attempts.

This study was designed to examine the types of stressful events that are related to adolescent suicidal behaviour. Adolescent inpatients who attempted suicide and a control group of high school students were compared on various types of stressors. The stressors were categorized according to their type (for example, discrete events versus chronic strains) and source (for example, family or friends). Compared to high school controls, adolescents who attempted suicide reported elevated levels of major negative events and exit events. Both chronic strains and discrete stressors were related to an increased severity of depression and suicidal ideation. The results support the notion that increased stress is related to adolescent suicidal behaviour. Different approaches to categorizing stress may improve the understanding of the relationship between stressful life events and suicide. Also, sex differences may influence the relationship between life stress and suicidal feelings.

Adolescent↗

Synthesis and in vitro evaluation of boronated uridine and glucose derivatives for boron neutron capture therapy.

The following boron-containing nucleoside and glucose derivatives have been synthesized as potential boron delivery agents for boron neutron capture therapy (BNCT): 2'-O-(o-carboran-1-ylmethyl)uridine (4a), 3'-O-(o-carboran-1-ylmethyl)uridine (4b), sodium 7-(uridin-2'-ylmethyl)dodecahydro-7,8-dicarba-++ +nido-undecaborate (5), 5'-O-(o-carboran-1-ylmethyl)uridine (9), and 3'-O-(o-carboran-1-ylmethyl)-D-glucose (13). In vitro cellular uptake studies were performed with F98 rat glioma cells. Following 16 h incubation, cellular boron concentrations were determined by direct current plasma atomic emission spectroscopy (DCP-AES). Boron concentrations ranged from 65 to 103 micrograms/g of cells for the neutral closo structures compared with 1.5 micrograms/g of cells for the charged nido species. Cellular uptake of sodium mercaptoundecahydro-closo-dodecaborate (BSH), the compound currently being used in Japan for the treatment of malignant brain tumors by BNCT, was 2 micrograms/g of cells.

Animals↗

Suicidal behavior and history of substance abuse.

Substance abuse is frequently associated with suicidal behavior. However, it is unclear to what degree substance abuse in a family member is related to suicide. In the present study, personal and family histories of substance abuse were examined in 716 psychiatric emergency room patients. Suicide attempters, suicide ideators, and nonsuicidal controls were compared across demographic, clinical, and substance abuse variables. Results showed that suicidal patients differed from nonsuicidal controls on many of the dependent variables. Suicidal patients were more likely to be depressed and report a history of previous suicidal tendencies. Also, alcohol and drug abuse occurred more frequently in suicidal patients. Furthermore, a family history of alcohol abuse was reported more often by suicidal than nonsuicidal patients. These patterns of substance abuse in suicidal patients were especially prominent among older subjects. Results are discussed in terms of the implications for identifying psychiatric emergency room patients at risk for suicide.

Adolescent↗

Determination of boron in tissues and cells using direct-current plasma atomic emission spectroscopy.

We have developed a safe, simple, and efficient method for boron determination by means of direct-current plasma atomic emission spectroscopy. Tissues were solubilized by using concentrated sulfuric acid and 70% hydrogen peroxide to digest the samples without the need of high temperatures and pressures. Boron cluster compounds could be measured with sensitivity, precision, and accuracy similar to those of boric acid standards. Results obtained with [(C2H5)3NH]2B12H12, Cs2B12H11SH.H2O, and C15H32B10O6 show that this analytical method is applicable to a variety of compounds with different chemical structures. A sensitivity of 0.1 ppm has been obtained with known standards alone and in a variety of tissue matrices including tumor, blood, liver, skin, and cell suspensions. The measurement of total boron by direct-current plasma atomic emission spectroscopy (DCP-AES) has been achieved with as little as 50 mg of tissue or as few as 5 x 10(7) cells. The procedure is applicable to the analysis of boron in the ppm range with a high degree of precision and accuracy.

Animals↗

Significance of observing no fluid at amniotomy.

Thirty patients with oligohydramnios observed at artificial rupture of membranes were studied to determine the significance of this finding. Fifteen were subsequently found to have meconium-stained amniotic fluid and 21 had abnormal fetal heart rate tracings. This clinical observation warrants close intrapartum surveillance and preparation for delivery.

Amniotic Fluid↗

Distinct and non-cross-reactive epitopes are recognized on B16 melanoma by LAK cells and anti-B16 monoclonal antibodies.

Two rat anti-B16 melanoma monoclonal antibodies (MoAb), designated IB16-6 and IB16-8, recognize an epitope expressed with high density on the surface of B16 parental cells and B16-F1, F10, F10FLR, and BL6 sublines. The purpose of this study was to define by means of cytolytic and clonogenic assays whether these MoAbs reacted with the same or distinct determinants as those recognized on B16 targets by lymphokine-activated killer (LAK) cells. Using 125I-labeled antibody and Scatchard analysis, the affinity constant (KA) of IB16-6 was determined to range from 5.6 to 9.4 x 10(8) liter/M and the number of receptor sites per B16 cell was 4.8 x 10(4) to 2.5 x 10(5). The effects of anti-B16 MoAb on LAK activity were determined by either preincubating 51Cr-labeled B16 target cells with varying concentrations of MoAb, followed by the cytolytic assay, or exposing unlabeled B16 cells to MoAb, and then carrying out a 10-day clonogenic assay. Over a wide range of antibody concentrations, IB16-6 and IB16-8 had minimal effects on LAK activity, and even at MoAb concentrations up to 1 mg there were no changes in target cell sensitivity or colony-forming ability. Enzymatic treatment of B16 melanoma cells with either trypsin or pronase completely removed the epitope recognized by MoAb IB16-6 but did not alter B16 sensitivity to LAK cells. These observations indicate that the LAK recognition unit was distinct from the epitope reactive with MoAb IB16-6 and that the B16 determinant(s) recognized by LAK cells is resistant to proteolytic enzymes. The molecular structure of each of these remains to be determined.

Animals↗

Pre-clinical studies on boron neutron capture therapy.

The present report provides an overview of the multidisciplinary research effort on BNCT that currently is in progress at The Ohio State University. Areas under investigation include the preparation of boron containing monoclonal antibodies, the synthesis of boron containing derivatives of promazines and phathalocyanines, the development of a rat model for the treatment of glioblastoma by means of BNCT, the design of an accelerator-based neutron irradiation facility, and 10B concentration measurements using alpha track autoradiographic methods. Progress in each of these areas is described and the direction of future research is indicated.

Animals↗

Boron neutron capture therapy: linkage of a boronated macromolecule to monoclonal antibodies directed against tumor-associated antigens.

Two new protein-binding polyhedral boron derivatives, isocyanatoundecahydro-closo-dodecaborate(2-) (1) and isocyanato(trimethylamino)octahydro-closo-decaborate(1 -) (2), were synthesized. These anionic isocyanates have long hydrolysis half-lives at pH 7 and react readily with primary or secondary aliphatic amines resulting in spontaneous urea linkage. Utilizing 1, 1100 boron atoms (7.3% boron by weight) were incorporated per molecule of a polyclonal antibody directed against human thymocytes (anti-thymocyte globulin) without denaturation. However, immunoreactivity of the conjugates was lost. Reaction of 1 and 2 with polylysine yielded boronated macromolecules containing 21-28% boron by weight (up to 2000 boron atoms per molecule). Polylysine boronated with 2 was successfully linked to antibody molecules employing the heterobifunctional linking molecules N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) and m-maleimidobenzoyl sulfosuccinimide ester (sulfo-MBS). Separation of the conjugated antibody from the free boronated macromolecules and unconjugated antibody molecules has been achieved by gel filtration on a Sephacryl S-300 column. By linking boronated polylysine to antibodies, greater than 10(3) boron atoms were incorporated with the attachment of this species to one or more sites on the antibody molecule. The resulting immunoconjugates contained greater than 10(3) boron atoms per molecule, retained their immunoreactivity, and potentially might be useful for the selective delivery of large numbers of boron atoms to tumor cells.

Animals↗

Electron spectroscopic imaging for high-resolution immunocytochemistry: use of boronated protein A.

In the present study we adapted electron spectroscopic imaging (ESI) for high-resolution immunocytochemistry. To accomplish this, we applied boronated protein A (B-pA) for indirect detection of specific antigenic sites using pre-embedding and post-embedding protocols. Isolated acinar cells were exposed to wheat germ agglutinin (WGA) and anti-WGA, followed by B-pA, to reveal WGA binding sites at the level of the plasma membrane. The cells were then embedded in Epon and unstained ultra-thin sections were examined by electron microscopy using the ESI mode. For post-embedding, ultra-thin sections of glutaraldehyde-fixed, Lowicryl-embedded pancreatic tissue were exposed to specific antibodies (anti-insulin or anti-amylase), followed by B-pA. The unstained sections were examined using the ESI mode. In both cases, boron was detected with high resolution either at the level of the plasma membrane of acinar cells, demonstrating WGA binding sites, or over secretory granules in pancreatic insulin-secreting cells or acinar cells, demonstrating insulin and amylase, respectively. These findings were compared to those obtained with the protein A-gold technique, and have demonstrated the analogy of both types of labeling. In addition, several control experiments assessed this novel approach. They have demonstrated the specificity of labeling and the high reactivity of B-pA, as well as its antibody-binding properties. Finally, electron energy loss spectral analysis confirmed the presence of boron in the tissue sections at sites where immunolabeling was detected. These results demonstrate that ESI is an appropriate approach for cytochemistry. Since the technique is based on detection of elements, spatial resolution is considered to be in the magnitude of 0.5 nm, which represents a major improvement in resolution over actual electron microscopic cytochemical techniques.

Animals↗

Intrapartum uterine rupture.

The association between diethylstilbestrol (DES) exposure in utero and uterine malformations resulting in poor reproductive performance is well established. A case is presented of uterine rupture in a patient exposed to DES in utero who had no known predisposing factors for uterine rupture.

Adult↗

Limits of sensitivity for the radioimmunodetection of colon cancer by means of a hand held gamma probe.

This study was undertaken to define the limits for the radioimmunodetection of minimal deposits of colorectal cancer cells using a hand held gamma probe. 125I labeled monoclonal antibody 17-1A and its F(ab')2 fragments were reacted in vitro with cells of the human colorectal cancer line SW 1116. The limits of sensitivity of the probe were determined by injecting doubling dilutions of 125I-antibody coated SW 1116 cells ranging from 10(7) to 3.9 x 10(4) subserosally at 2 cm intervals into 60 cm segments of freshly obtained autopsy or surgical specimens of human colon. A linear relationship was observed between the number of cells injected and the number of counts obtained with either the probe or well counter. As few as 6.25 x 10(5) 125I-antibody coated cells (less than 1 mm3) were detected under experimentally defined conditions by an earlier version of the probe, and 3.9 x 10(4) coated cells (much less than 1 mm3) could be detected by the currently available model. Although the count rates were less than 5% of those obtained by well counter, nevertheless, these were 10-25 times greater than background and allowed the detection of tumor cell deposits that otherwise would not have been discernible by either palpation or external scintigraphy. These findings, in conjunction with ongoing clinical studies, suggest that the hand held gamma probe may increase the usefulness of monoclonal antibodies for the radioimmunodetection of cancer.

Antibodies, Monoclonal↗

Effects of brackets and ties on stiffness of an arch wire.

Beam theory was used to evaluate the stiffness of a simulated orthodontic model as affected by the type of bracket, interbracket distance, type of ligature tie, and size of segment. For a given deflection, the model generated greater force (increased stiffness) as the beam constant (N) increased. N increased as interbracket distance increased. Metal ties were as rigid or more rigid than o-rings. Four bracket segments were more rigid than two-bracket segments when tied with o-rings but not metal ligatures. Values of N of Lewis and narrow twin brackets with metal ties were similar and greater than the N of wide twin and medium single brackets. Wide twin brackets were more rigid than others with o-rings.

Elasticity↗