PubMed HealthSearch

Biomedical subjects

F C Miller

Publications and source records attributed to F C Miller.

At least 19 recordsLinked to original sources

New monoclonal antibodies identify the glycoprotein carrying the CA 125 epitope.

CA 125 is an antigenic determinant located on the surface of ovarian carcinoma cells and elevated in the serum of greater than 90% of patients with carcinoma. The antigen, derived from the ovarian epithelium, has been described as a mucinlike glycoprotein greater than 200 kd. To date little is known of the metabolic regulation or expression of this antigen in either normal or neoplastic tissues. New monoclonal antibodies that we describe here recognize both unique and similar epitopes to OC 125. These reagents may allow for a more complete definition of the structure and expression of the CA 125 complex. These antibodies recognize high-molecular weight (greater than 200 kd) subspecies and a lower-molecular-weight (68 kd) subspecies of the antigen and identify it in the cytoplasm and the extracellular matrix of CA 125-producing cells.

Animals

The N-terminal and C-terminal portions of the atrial natriuretic factor prohormone increase during preeclampsia.

The influence of preeclampsia on the circulating concentrations of the 28-amino-acid carboxy terminus (C-terminus) (i.e., atrial natriuretic factor) and the amino terminus (N-terminus) of the 126-amino-acid atrial natriuretic factor prohormone (pro ANF) was studied in the third trimester with the use of three specific radioimmunoassays that recognize: (1) atrial natriuretic factor (i.e., amino acids 99 to 126), (2) the whole 98-amino-acid N-terminus, and (3) amino acids 31 to 67 from the midportion of the N-terminus of the prohormone. The C-terminus was significantly increased (p less than 0.001) in the third trimester in women with preeclampsia, the mean +/- SEM of 15 subjects was 150 +/- 7 pg/ml versus 89 +/- 7 pg/ml in the third trimester in 12 women during normal pregnancies and 65 +/- 2 pg/ml in 19 healthy nonpregnant women. The whole 98-amino-acid N-terminus, likewise, was significantly increased (p less than 0.001) in women with preeclampsia to 4706 +/- 629 pg/ml versus 2160 +/- 79 pg/ml in women in the third trimester of normal pregnancies and versus the circulating concentration of 1847 +/- 127 pg/ml in healthy nonpregnant women. ProANF 31 to 67 mean circulating concentration in preeclampsia was 4638 +/- 725 pg/ml, which was also significantly (p less than 0.001) increased compared with its mean circulating concentration in the third trimester of normal pregnancy of 1758 +/- 83 pg/ml or that in healthy nonpregnant women (1400 +/- 105 pg/ml). The circulating concentrations of both the N-terminus and C-terminus of the atrial natriuretic factor prohormone decreased within 24 hours after delivery in contrast to a normal pregnancy in which they both increase post partum. These results indicate a marked difference in the metabolism of both the N-terminus and the C-terminus of the atrial natriuretic factor prohormone in women with preeclampsia versus that in women with normal pregnancies or that in healthy nonpregnant women.

Adolescent

Use of monoclonal antibodies with neutralizing effects on toxic antigens from human bacterial plaque to detect specific bacteria by colony blotting.

Inflammatory periodontal diseases are provoked by bacteria which adhere to teeth at the gingival margin and form plaques containing toxins detectable by their effect on mammalian cells in culture. The aim of this study was to make toxin-neutralizing monoclonal antibodies and determine whether they detect antigen in specific oral bacteria. Bacterial plaque was collected from teeth and homogenized, and the fluid phase (plaque extract) was boiled or first fractionated over Sephacryl S-300. Hybridomas from immunized mice secreted immunoglobulin M (IgM) antibodies which reacted to plaque antigens. Neutralization was detected by an increase in the growth of HL60 cells which were exposed to plaque toxins in the presence of IgM from hybridoma culture or ascitic fluids. However, the neutralization was obvious only when the plaque toxins reduced growth by 50% or less. Plaque toxin preparations were found to contain proteases which hydrolyzed all of the IgM in ascitic fluids within 24 h. Replenishing the IgM daily preserved protection compared with protection from IgM from other hybridomas or saline only. The decrease in the specific activity of plaque proteins caused by replenishing one such antibody (3hE5) was 2.5-fold compared with activity with unreplenished 3hE5, 3.8-fold compared with activity with saline only, and 10.7-fold compared with activity with replenished, unrelated antibody. The neutralizing IgM detected an array of 14,000- to 22,000-molecular-weight antigens. The native toxins may be aggregates of these antigens, or the array may indicate fragments of an undetected, larger antigen or a common, nonpeptide adduct. Only 0.5 to 0.8% of the bacteria from sites with periodontitis and grown on blood agar contained antigen. One group of reactive bacteria was identified as Actinomyces odontolyticus serotype I. Other isolates were identified as Staphylococcus epidermidis, but antigen disappeared from the these isolates within 6 weeks of subculture. Epitope-containing antigens were also found in streptococcal and Eikenella isolates, and it is likely that the antigens from only some of these bacteria are toxic.

Animals

Distribution of CA 125 in embryonic tissues and adult derivatives of the fetal periderm.

New murine monoclonal antibodies to a partially purified CA 125 antigen were developed and identified as M 2 and M 11. With immunohistochemical techniques, these new antibodies and OC 125 antibody were used to search for CA 125 in embryonic tissues and adult apocrine sweat glands and mammary glands. The embryonic skin, the periderm, expressed CA 125 antigen and its adult derivatives, the mammary glands and apocrine sweat glands, expressed CA 125 while in the active state of secretion. In a 6-week-old formalin-fixed and paraffin-embedded ectopic embryo specimen, antibodies M 2 and M 11 recognized CA 125 in the periderm, the notochord, the myocardium, the pericardium, the gastroenteric tract, enteric duct remnants in the umbilical cord (vitelline and allantoic ducts), the mesonephric duct, and the amnion. OC 125 staining of these formalin-fixed specimens was either very faint or absent. In a formalin-fixed and paraffin-embedded specimen of apocrine sweat glands from the axilla, antibodies M 2 and M 11 detected CA 125 antigen intracellularly in the secretory cells. Again no staining was observed with OC 125 antibody. In a frozen and acetone-fixed specimen of lactating mammary glands, antibodies M 2 and OC 125 detected CA 125 antigen intraductally. Colostrum and milk collected from 25 mothers at various stages post partum had mean CA 125 levels of 34,213 U/ml in colostrum, 1469 U/ml at 3 to 7 days, and 105 U/ml at 5 to 26 weeks.

Amnion

Increase in the plasma levels of the N-terminal and C-terminal portions of the prohormone of atrial natriuretic factor during normal pregnancy.

The influence of pregnancy on the circulating concentrations of atrial natriuretic factor, the 28 amino acid carboxy (C)-terminal end of the 126 amino acid atrial natriuretic factor prohormone, and the amino (N)-terminus of the prohormone was studied with three specific radioimmunoassays recognizing: (1) atrial natriuretic factor (i.e., amino acids 99 through 126), (2) the 98 amino acid N-terminus, and (3) amino acids 31 through 67 from the midportion of the N-terminus of the prohormone. Plasma atrial natriuretic factor in normal pregnant women gradually increased as pregnancy progressed, with the mean +/- SEM being 58 +/- 4 pg/ml in the first trimester, 74 +/- 5 pg/ml in the second trimester, and 89 +/- 7 pg/ml in the third trimester. Likewise, proatrial natriuretic factor 31 through 67 increased from 1421 +/- 76 pg/ml (first trimester) to 1509 +/- 84 pg/ml (second trimester) to 1758 +/- 83 pg/ml in the third trimester, whereas the whole N-terminus of the prohormone increased from 1804 +/- 98 pg/ml (first trimester) to 1909 +/- 111 pg/ml (second trimester) to 2160 +/- 79 pg/ml in the third trimester. These results suggest that release of the N-terminus of the prohormone, as well as atrial natriuretic factor, increases with the rise in blood volume associated with a normal pregnancy. The circulating concentrations of both the C-terminus and N-terminus of the atrial natriuretic factor prohormone increased further in the 48 hours after delivery. Because both the C-terminus and N-terminus of the atrial natriuretic factor prohormone contain diuresis-producing peptides, these results suggest that postpartum diuresis may be mediated by these peptides.

Analysis of Variance

Oxygen desaturation in women in labor.

Oxygen saturation and end-tidal CO2 tension were monitored in 15 healthy women during labor. Oxygen saturation was determined with a pulse oximeter and end-tidal CO2 with a CO2 monitor. Fetal heart rate, uterine contractions and maternal blood pressure were also monitored. End-tidal CO2 tension was followed to determine if falls in oxygen saturation during labor were related to hyperventilation. Ten of the 15 patients exhibited periods of oxygen saturation of less than 90%. End-tidal CO2 was consistently low, usually less than 30 mm Hg. Most, but not all (7 of 10), of the patients who showed desaturation had received narcotics. There were often periods of apnea and/or shallow respirations between contractions. These aberrations and hyperventilation-induced hypocarbia were probably the cause of the oxygen desaturation. No changes in fetal heart rate or low Apgar scores were noted.

Adolescent

The use and interaction of permanent pacemakers and the automatic implantable cardioverter defibrillator.

The adverse interactions of permanent pacemakers and automatic implantable cardioverter defibrillators (AICD) were studied in nine patients in whom both devices were implanted. Both unipolar and bipolar pacemakers were evaluated. The permanent pacemakers were also used to do noninvasive electrophysiological studies and to induce ventricular fibrillation. Undersensing of ventricular fibrillation by the permanent pacemakers caused inappropriate pacemaker stimuli, which caused undersensing of ventricular fibrillation by the AICD in three of four patients with unipolar pacemakers. After an AICD discharge, pacemaker noncapture was seen in eight of 22 episodes for an average 4.9 seconds and inability to sense was seen in 11 of 20 episodes for an average 9.0 seconds. Counting of pacemaker stimuli and QRS by the AICD caused inappropriate discharges. Noninvasive electrophysiological testing by the pacemakers correlated with invasive testing. Furthermore, induction of ventricular fibrillation was successful in four of five patients attempted, though requiring long bursts at high outputs at the shortest cycle lengths obtainable by these pacemakers. Operation of the AICD and permanent pacemakers must be clearly understood to avoid adverse interactions of these devices.

Electric Countershock

Noninvasive electrophysiologic study using standard permanent pacemakers in patients with spontaneous sustained ventricular tachycardia or ventricular fibrillation.

Permanent pacemakers capable of noninvasive electrophysiologic testing were used to study and treat 26 patients with spontaneous sustained ventricular tachycardia (VT) or fibrillation (VF). One hundred nine episodes of sustained VT or VF were induced in these patients. In 8 patients spontaneous VT was reverted by noninvasive means. Drug changes based on noninvasive testing were made in 12 patients. In the 1- to 67-month follow-up period, drug therapy based on noninvasive electrophysiologic testing was predictive of outcome in patients with spontaneous arrhythmias. Thus, noninvasive electrophysiologic testing using permanent pacemakers is a useful method for studying and treating patients with recurrent sustained ventricular arrhythmias.

Cardiac Pacing, Artificial

Noninvasive detection of coronary artery patency using continuous ST-segment monitoring.

Continuous ST-segment Holter recordings were analyzed from 46 patients with acute myocardial infarction (AMI) receiving intracoronary streptokinase (SK) during the first 48 hours of hospitalization. Changes in ST deviation and the time periods of these changes were quantitated and correlated with angiographic evidence of reperfusion. Thirty-six patients had total occlusion of the infarct vessel and 10 had subtotal occlusion. Of the 36 vessels that were totally occluded, 19 were reperfused and 17 were not. In patients in whom reperfusion was successful, an ST steady state was achieved 55 +/- 32 minutes after SK administration. In patients in whom it was not successful, a steady state was achieved in 219 +/- 141 minutes (p less than 0.001). Achievement of steady state within 100 minutes after SK reperfusion indicated successful reperfusion with 89% sensitivity and 82% specificity. All patients with subtotal occlusion achieved an ST steady state before SK infusion. No patient with total occlusion achieved a steady state before SK. Achievement of ST steady state before SK infusion was 100% sensitive and 100% specific for subtotal occlusion at initial angiography. Continuous, quantitative ST-segment analysis is a sensitive and specific noninvasive technique for following coronary artery patency during AMI.

Coronary Vessels

Ventricular arrhythmias during reperfusion.

Accelerated idioventricular rhythm has been used as a marker for coronary reperfusion. The incidence of accelerated idioventricular rhythm and ventricular tachycardia was evaluated in 52 consecutive patients undergoing thrombolysis with intracoronary streptokinase during acute myocardial infarction. Complete 12-hour Holter recordings during and after intracoronary streptokinase were obtained in 39 patients. Reperfusion was documented in 17 patients (44%), no reperfusion in 14 (36%), and subtotal occlusion in eight (20%). Accelerated idioventricular rhythm occurred in 83%, 57%, and 63% of patients by group, respectively (p greater than 0.05). Ventricular tachycardia occurred in 100%, 71%, and 100% of patients by group, respectively (p less than 0.05). These data demonstrate that accelerated idioventricular rhythm is not specific for reperfusion and cannot be used as a marker for this event, and that ventricular tachycardia is more common with reperfusion and subtotal occlusion.

Cardiac Catheterization

The evaluation of uterine activity: a comparative analysis.

In this study a comparison is made between the most widely accepted method of expressing uterine activity, Montevideo units, and an automated on-line method expressed as uterine activity units. Although the actual numerical expression differs, the percentage of variation when the two values are compared is small at various phases of labor. The variation between the methods for uterine activity required to progress from 4 to 6 cm cervical dilatation and from 6 to 10 cm cervical dilatation is less than 5%. Both methods closely agree on the actual expression of uterine activity or uterine work.

Amniotic Fluid

Continuous intrapartum monitoring of fetal scalp pH.

Forty patients were monitored intrapartum with a continuous fetal scalp tissue pH electrode in the mean time of 2.39 hours. The monitoring records were considered "accurate" with good correlation to the intermittent fetal scalp capillary pH values in 76.9 per cent. The correlation coefficient was 0.74. The "accuracy" improved in the latter 23 cases to 87 per cent with a correlation coefficient of 0.82. This improvement was probably due to modification of the application technique, as well as to a new calibration method at 37 degrees. Continuous fetal scalp pH monitoring was clinically useful in 65 per cent, it was partially useful in 20 per cent, but of no value in 15 per cent of the patients studied. There were no apparent maternal complications with the use of this technique and 38 of the infants had no sequelae. Two infants had complications: one developed inflammation of the electrode site. This was treated with antibiotics. One electrode broke during the application and a fragment of the electrode tip remained in the fetal scalp. All the infants were grossly normal and there was a good correlation between the continuous pH readings and the immediate neonatal outcome.

Adult

The bupivacaine paracervical block in labor and its effect on quantitative uterine activity.

This study utilized internal fetal monitoring and an on-line voltage control oscillator for measurement of uterine activity unit (UAU) determination in patients who received a paracervical block (PCB) with the use of bupivacaine hydrochloride (Marcaine). The total dose of 25 mg (5 cc/side) of 0.25% bupivacaine used for PCB in 32 patients produced no ill effects to the fetus, as reflected by baseline fetal heart rate (FHR), beat-to-beat variablity, or Apgar scores. No adverse maternal effects were noted, and anesthesia was rated good or excellent in 81% of patients. Rate of cervical dilation remained the same or increased in 29 of 32 patients. Quantitative UAUs showed a significant decrease in the third 10-minute interval after block in primiparas, but no significant change in multiparas or in the group taken as a whole. Total UAUs before versus after PCB for either group or taken together were not statistically different. A decreasing trend in UAUs after PCB versus a positive regression line from activity prior to the block was noted.

Anesthesia, Local