Biomedical subjects
D A Wing
Publications and source records attributed to D A Wing.
A comparison of intermittent vaginal administration of misoprostol with continuous dinoprostone for cervical ripening and labor induction.
OBJECTIVE: Our purpose was to compare the effect of vaginal administration of misoprostol (Cytotec) with that of dinoprostone (Cervidil) on cervical ripening and labor induction. STUDY DESIGN: Two hundred patients with indications for induction of labor and unfavorable cervical examinations were randomly assigned to receive vaginally administered misoprostol (prostaglandin E1) or the dinoprostone (prostaglandin E2) vaginal insert. Twenty-five microgram tablets of misoprostol were placed in the posterior vaginal fornix every 4 hours for a maximum of six doses. Additional misoprostol was not given after either spontaneous rupture of membranes, adequate cervical ripening (Bishop score of > or = 8 or cervical dilatation of > or = 3 cm), or beginning of active labor. The vaginal insert, Cervidil, containing 10 mg of dinoprostone in a timed-release preparation was placed in the posterior vaginal formix for a maximum period of 24 hours. The vaginal insert was removed for spontaneous rupture of membranes, entry into active labor, adequate cervical ripening, or abnormality of uterine contractile pattern or fetal cardiac activity. RESULTS: Of the 200 patients enrolled, 99 were randomized to misoprostol and 101 to dinoprostone. The average interval from start of induction to vaginal delivery was 1 hour shorter in the misoprostol group (1296.7 +/- 722.1 minutes) than in the dinoprostone group (1360.0 +/- 792.0 minutes), but this difference was not statistically significant (p = 0.97). Oxytocin augmentation of labor was used in 50 (50.5%) misoprostol-treated patients and 43 (43.5%) dinoprostone-treated patients (relative risk 1.14, 95% confidence interval 0.86 to 1.51, p = 0.35). There were no significant differences between routes of delivery with misoprostol or dinoprostone. Overall, 38 patients (19.3%) had cesarean deliveries. There was a significantly lower prevalence of tachysystole (six or more uterine contractions in a 10-minute window for two consecutive 10-minute periods) in the misoprostol group (7.1%) than in the dinoprostone group (18.4%) (relative risk 0.52, 95% confidence interval 0.31 to 0.89, p = 0.02). There were no significant differences in frequency of uterine hyperstimulation or hypertonus. Abnormal fetal heart rate tracings were found in 23 (23.2%) of misoprostol-treated patients and 35 (35.7%) of dinoprostone-treated patients (relative risk 0.73, 95% confidence interval 0.52 to 1.01, p = 0.0546). No significant differences were found in meconium passage, 1- or 5-minute Apgar scores < 7, neonatal resuscitations, or admissions to the neonatal intensive care unit between the two groups. CONCLUSIONS: Vaginally administered misoprostol is as effective as dinoprostone for cervical ripening and the induction of labor. Mean time intervals to delivery, need for oxytocin augmentation, and routes of delivery were similar between the two groups. Incidence of uterine tachysystole with misoprostol every 4 hours was significantly less than with dinoprostone.
Usefulness of coagulation studies and blood banking in patients with symptomatic placenta previa.
We conducted this study to ascertain the usefulness of coagulation studies and blood bank utilization in the patient with symptomatic placenta previa. During a 2-year interval, 97 patients with uterine bleeding due to placenta previa diagnosed > or = 24 weeks' gestation were evaluated. The following studies were routinely obtained: complete blood count including platelet count, fibrinogen, prothrombin time, and a Kleihauer-Betke test. A type and cross-match was sent to the blood bank, and blood availability was maintained for all patients throughout the course of hospitalization. For 92 of 97 patients the laboratory values and need for immediate blood availability were analyzed. No abnormal prothrombin times or Kleihauer-Betke tests were found. There was one low fibrinogen value in a patient with a normal complete blood count. The initial hematocrits ranged from 16.5 to 40.0%, and the initial hemoglobins ranged from 5.5 to 14.1 mg/dL. Five patients had platelet counts of < or = 150 k/mm3 (range 75 to 149 k/mm3). Fourteen patients (14.6%) required transfusion, two received their transfusion antepartum and 12 received perioperative transfusion with a cesarean delivery. During this time period, only two patients required emergent delivery within 1 hr of presentation to the hospital. One patient had delayed seeking medical attention for more than 3 hr prior to admission despite significant hemorrhage. Coagulation studies and Kleihauer-Betke tests have limited utility in the symptomatic patient with uterine bleeding from placenta previa. Continuous availability of cross-matched blood in the antepartum period appears unnecessary as no patients in this investigation were transfused emergently.
A comparison of differing dosing regimens of vaginally administered misoprostol for preinduction cervical ripening and labor induction.
OBJECTIVE: Our purpose was to compare two dosing regimens of vaginally administered misoprostol for preinduction cervical ripening and induction of labor. STUDY DESIGN: Five hundred twenty-two patients with indications for induction of labor and unfavorable cervices were randomly assigned to one of two dosing regimens of vaginally administered misoprostol. Twenty-five microgram tablets of misoprostol were placed in the posterior vaginal fornix either every 3 hours to a maximum of eight doses or every 6 hours to a maximum of four doses. The maximal period of cervical ripening was 24 hours regardless of the number of misoprostol doses administered. Medication was not given after either spontaneous rupture of membranes or the beginning of active labor. RESULTS: Among 522 patients enrolled, 261 were randomized to receive misoprostol every 3 hours and 261 to receive misoprostol every 6 hours. The average interval from start of induction to vaginal delivery was shorter in the 3-hour dosing group (1311.74 +/- 785.14 minutes) than in the 6-hour dosing group (1476.96 +/- 805.30 minutes) (p < 0.05). Oxytocin augmentation of labor occurred more commonly in the 6-hour dosing group (51.4%) than in the 3-hour dosing group (41.8%) (p < 0.05) [corrected]. There were no significant differences between routes of delivery. Overall, 108 patients (20.8%) were delivered by cesarean section. There was a slightly higher prevalence of tachysystole (six or more uterine contractions in a 10-minute window for two consecutive 10-minute periods) in the 3-hour group (14.6%) than in the 6-hour group (11.2%), but this difference was not statistically different. There were no significant differences in the frequency of uterine hyperstimulation or hypertonus. There was no significant difference between groups in the frequency of abnormal fetal heart rate tracings, meconium passage, 1- or 5-minute Apgar scores < 7, neonatal resuscitations, or admissions to the neonatal intensive care unit. CONCLUSIONS: Vaginally administered misoprostol is an effective agent for cervical ripening and induction of labor. Patients with the 6-hour dosing schedule had longer intervals to delivery, more frequently required oxytocin augmentation, and had more failed inductions than did patients with 3-hour dosing. Further investigation to characterize the safety of misoprostol is needed.
How frequently should the amniotic fluid index be performed during the course of antepartum testing?
OBJECTIVE: Our purpose was to evaluate the need for frequent amniotic fluid volume assessments in our antepartum testing unit. STUDY DESIGN: In a retrospective analysis of data accumulated over 1 year in our antepartum testing unit amniotic fluid index values performed at 3- to 4-day intervals were compared with follow-up values. Of 11,827 amniotic fluid index values, there were 6291 with follow-up values within 4 days. The results were stratified on the basis of the subsequent amniotic fluid index value and estimated gestational age. Comparisons were made relating to amniotic fluid index testing intervals of 4 versus 7 days. RESULTS: Patients with an amniotic fluid index > 8 cm had a 2.3% chance (128/5677) of having oligohydramnios (amniotic fluid index < or = 5.0 cm) in the next 4 days. Those patients with low-normal amniotic fluid index values (5 to 8 cm) had a 16.2% chance (96/593) of having oligohydramnios in the next 4 days. There were few patients with an amniotic fluid index < or = 5 cm who had subsequent amniotic fluid index values measured. Patients with an amniotic fluid index > 8 cm had a 2.2% chance (156/6946) of having oligohydramnios within 7 days, and those with low-normal amniotic fluid index values had a 16.3% chance (105/643) of having oligohydramnios with 7 days. Stratifying the results by gestational age reveals that patients at > or = 41 weeks of gestation had a 23.3% chance of having oligohydramnios within 4 days if the current amniotic fluid index was found to be 5 to 8 cm and a 7.4% chance if the current amniotic fluid index was found to be normal. Term (estimated gestational age of 37 to 40 weeks) patients had a similar risk of oligohydramnios in 4 days if the amniotic fluid index was low-normal (17.8%) but a risk of 3.6% if the amniotic fluid index was normal. CONCLUSIONS: For patients at < 41 weeks of gestation undergoing antepartum testing, weekly assessments of amniotic fluid index is probably adequate if the initial measurement is in the normal range (> or = 8 cm) because the risk of having oligohydramnios within 7 days is low (2.2%). For patients at < 41 weeks of gestation whose initial amniotic fluid index measurement is in the low-normal range (5 to 8 cm), a scheme of twice-weekly assessment is justified on the basis of a higher risk for an amniotic fluid index < or = 5 cm within 4 days (12.3%). For all patients at > or = 41 weeks of gestation, twice-weekly amniotic fluid index assessments are recommended regardless of the initial measurement.
Management of the symptomatic placenta previa: a randomized, controlled trial of inpatient versus outpatient expectant management.
OBJECTIVE: Our purpose was to determine the safety, efficacy, and costs of inpatient and outpatient management of symptomatic placenta previa. STUDY DESIGN: Fifty-three women with the initial diagnosis of placenta previa at 24 to 36 weeks' gestation who required hospitalization for vaginal bleeding were stabilized and then randomized to receive either inpatient or outpatient expectant management. Twenty-seven inpatients were placed at bed rest with minimal ambulation, received weekly corticosteroids until 32 weeks of gestation, and underwent ultrasonographic examination at 2-week intervals to assess fetal growth and placental location. Twenty-six outpatients were discharged home after > or = 72 hours of hospitalization. Each week they also received corticosteroids, until 32 weeks' gestation, and ultrasonographic evaluations. Outpatients with recurrent bleeding were readmitted for evaluation. All subjects who reached 36 weeks' gestation with persistent placenta previa underwent amniocentesis. When fetal lung maturity was present, cesarean delivery was electively performed. RESULTS: There were insignificant differences between inpatients and outpatients for mean age, parity, race, type of previa (complete or partial), number of prior vaginal bleeding episodes, and initial hemoglobin value. The mean estimated gestational age at enrollment was 29.1 +/- 3.1 (SD) weeks for inpatients and 29.9 +/- 3.1 weeks for outpatients. In eight patients the placenta was found to no longer cover the internal os by 36 weeks' gestation. There were seven patients in each group who did not complete the protocol for initial treatment assignment. The average estimated gestational age at delivery for the inpatients was 34.5 +/- 2.4 weeks and 34.6 +/- 2.3 weeks for the outpatients (p = 0.90), whereas the mean birth weights were 2413.7 +/- 642.7 gm and 2607.8 +/- 587.1 gm, respectively (p = 0.28). Thirty-three patients (62.3%) had recurrent episodes of bleeding, with 26 requiring expeditious cesarean delivery. Four (14.8%) inpatients and one (3.7%) outpatient required blood transfusion (p = 0.67). There was no difference in neonatal morbidity (defined as the presence of respiratory distress syndrome, intracranial hemorrhage, or culture-proved sepsis) between the two groups (relative risk 1.16, 95% confidence interval 0.66 to 2.02). There were no neonatal deaths. The mean number of maternal hospital days differed significantly between the two groups: inpatients required an average of 28.6 +/- 20.3 days and outpatients remained hospitalized for an average of 10.1 +/- 8.5 days (p < 0.0001). Cost analysis based on maternal hospital days reveals a net savings of +15,080 per patient if women with symptomatic placenta previa initially diagnosed before 37 weeks' gestation are treated as outpatients. CONCLUSIONS: For selected patients, outpatient management of symptomatic placenta previa appears to be an acceptable alternative to traditional conservative expectant inpatient management.
A comparison of misoprostol and prostaglandin E2 gel for preinduction cervical ripening and labor induction.
OBJECTIVE: Our purpose was to compare the safety and efficacy of intravaginal misoprostol versus intracervical prostaglandin E2 (dinoprostone) gel for preinduction cervical ripening and induction of labor. STUDY DESIGN: One hundred thirty-five patients with indications for induction of labor and unfavorable cervices were randomly assigned to receive either intravaginal misoprostol or intracervical dinoprostone. Fifty microgram tablets of misoprostol were placed in the posterior vaginal fornix every 3 hours for a maximum of six doses. Prostaglandin E2 in gel form, 0.5 mg, was placed into the endocervix every 6 hours for a maximum of three doses. Medication was not given after either spontaneous rupture of membranes or beginning of active labor. RESULTS: Among 135 patients enrolled, 68 received misoprostol and 67 received dinoprostone. The average interval from start of induction to vaginal delivery was shorter in the misoprostol group (903.3 +/- 482.1 minutes) than in the dinoprostone group (1410.9 +/- 869.1 minutes) (p < 0.001). Oxytocin augmentation of labor occurred more often in the dinoprostone group (65.7%) than in the misoprostol group (33.8%) (p < 0.001). There were no significant differences between routes of delivery. Ten of the misoprostol-treated patients (14.7%) and 13 of the dinoprostone-treated patients (19.4%) had cesarean deliveries. There was a higher prevalence of tachysystole (six or more uterine contractions in a 10-minute window for two consecutive 10-minute periods) in the misoprostol group (36.7%) than in the dinoprostone group (11.9%) (p < 0.001). However, there were no significant differences in frequency of uterine hyperstimulation or hypertonus. There was a higher prevalence of meconium passage in the misoprostol group (27.9%) than in the dinoprostone group (10.5%) (p < 0.05). There was no significant difference in frequency of abnormal fetal heart rate tracings, 1- or 5-minute Apgar scores < 7, neonatal resuscitations, or admissions to the neonatal intensive care unit between the two groups. CONCLUSIONS: Vaginally administered misoprostol is an effective agent for cervical ripening and induction of labor; however when given at this dosage, it is associated with a higher prevalence of tachysystole and meconium passage than is dinoprostone. Further studies to compare the safety of misoprostol to that of dinoprostone and to delineate an optimal dosing regimen for misoprostol are needed.
Misoprostol: an effective agent for cervical ripening and labor induction.
OBJECTIVE: Our purpose was to compare the safety and efficacy of intravaginal misoprostol versus intracervical prostaglandin E2 gel (dinoprostone) for preinduction cervical ripening and induction of labor. STUDY DESIGN: Two hundred seventy-six patients with indications for induction of labor and unfavorable cervices were randomly assigned to receive either intravaginal misoprostol or intracervical dinoprostone. Twenty-five micrograms of misoprostol were placed in the posterior vaginal fornix every 3 hours, with a potential maximum of eight doses. Prostaglandin E2 in gel form, 0.5 mg, was placed in the endocervix every 6 hours, with a maximum of three doses. Further medication was withheld with the occurrence of spontaneous rupture of membranes, entry into active phase of labor, or a "prolonged contraction response." RESULTS: Among those evaluated, 138 received misoprostol and 137 received dinoprostone. The average interval from start of induction to vaginal delivery was shorter in the misoprostol group (1323.0 +/- 844.4 minutes) than in the dinoprostone group (1532.4 +/- 706.5 minutes) (p < 0.05). Need for oxytocin augmentation of labor occurred more commonly in the dinoprostone group (72.6%) than in the misoprostol group (45.7%) (p < 0.0001). There were no significant differences in the routes of delivery. Twenty-eight of the misoprostol-treated patients (20.3%) and thirty-eight of the dinoprostone-treated patients (27.7%) required abdominal delivery. Complications such as uterine tachysystole and thick meconium passage occurred with similar frequency in the two treatment groups. CONCLUSIONS: Intravaginal administration of misoprostol appears to be as effective as intracervical dinoprostone for cervical ripening and labor induction. Complications associated with prostaglandin administration were not statistically different between the two treatment groups. The cost of misoprostol ($0.36/100 micrograms) is much less than that of dinoprostone ($75/0.5 mg).
Outpatient treatment of pyelonephritis in pregnancy: a randomized controlled trial.
OBJECTIVE: To compare the safety and efficacy of outpatient and inpatient treatment of pyelonephritis in pregnancy. METHODS: We performed a randomized controlled trial of pregnant women with pyelonephritis before 24 weeks' estimated gestational age, comparing inpatient and outpatient treatment. Sixty inpatients received cefazolin intravenously until afebrile for 48 hours, and 60 outpatients received two injections of ceftriaxone intramuscularly. All patients completed a 10-day course of oral cephalexin. We performed a urine culture 5-14 days after completion of therapy. RESULTS: The two groups were similar with respect to age, parity, temperature, estimated gestational age, initial white blood cell count, and incidence of bacteremia. Escherichia coli was the major uropathogen isolated (86% of cultures, 95 of 111). Twelve percent (13 of 111) of bacteria were resistant to cefazolin. Eleven outpatients and 12 inpatients had positive urine cultures after therapy (relative risk 0.9, 95% confidence interval 0.4-1.9). Three patients in each group had recurrent pyelonephritis. We switched six inpatients to gentamicin because of a worsening clinical picture (two) or a prolonged febrile course (four); no outpatients required a change in antibiotic (Fisher exact test, P = .03). One preterm delivery occurred in an inpatient with recurrent pyelonephritis. CONCLUSION: Outpatient antibiotic therapy is effective and safe in selected pregnant women with pyelonephritis.
A comparison of propylthiouracil versus methimazole in the treatment of hyperthyroidism in pregnancy.
OBJECTIVE: Our purpose was to demonstrate that propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism during pregnancy. STUDY DESIGN: Between 1974 and 1990 records were available on 185 pregnant patients with a history or diagnosis of hyperthyroidism. Ninety-nine patients were treated with propylthiouracil and 36 with methimazole. The response to therapy was compared with respect to the time to normalization of the free thyroxine index and the incidences of congenital anomalies and hypothyroidism. RESULTS: The time to normalization of the free thyroxine index was compared in the two groups by means of survival analysis. The median time to normalization of the free thyroxine index on propylthiouracil and methimazole was 7 and 8 weeks, respectively (p = 0.34, log-rank test). The incidence of major congenital malformations in mothers treated with propylthiouracil and methimazole was 3.0% and 2.7%, respectively. No neonatal scalp defects were seen. One infant was overtly hypothyroid at delivery. CONCLUSION: Propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism in pregnancy.
Low birth weight and preeclampsia in pregnancies complicated by hyperthyroidism.
OBJECTIVE: To determine whether control of hyperthyroidism during pregnancy reduces the risk of low birth weight infants and severe preeclampsia. METHODS: Labor, delivery, and postpartum records of 181 hyperthyroid women were reviewed for maternal and fetal outcomes. Subjects were separated into three groups based on their thyroid status: controlled (n = 34), including women who were euthyroid at presentation and delivery; controlled during pregnancy (n = 90), including women who were hyperthyroid at presentation and euthyroid at delivery; and uncontrolled (n = 57), including women who were hyperthyroid at presentation and delivery. RESULTS: The risk of low birth weight infants was 0.74 (95% confidence interval [CI] 0.18-3.08) among controlled women, 2.36 (95% CI 1.36-4.12) among women who were controlled during pregnancy, and 9.24 (95% CI 5.47-15.6) among women who were uncontrolled during pregnancy compared to the incidence among nonhyperthyroid mothers. The risk of severe preeclampsia was significantly higher (odds ratio 4.74, 95% CI 1.14-19.7) among uncontrolled women compared with those who were controlled during their pregnancies. Elevated TSH-receptor antibody levels were not related to preeclampsia. Maternal thioamide therapy did not adversely affect neonatal outcomes. CONCLUSION: Lack of control of hyperthyroidism significantly increases the risk of low birth weight infants and severe preeclampsia.
Modifiers of mercaptopyruvate sulfurtransferase catalyzed conversion of cyanide to thiocyanate in vitro.
The enzyme mercaptopyruvate sulfurtransferase appears to play an important role in the in vivo detoxification of cyanide. It does so by transferring sulfur to cyanide to produce thiocyanate, which is less toxic and may be excreted through the kidney. Several compounds were tested for their ability to affect the rate of enzyme catalyzed thiocyanate formation in vitro. The studies were carried out using both a partially purified bovine kidney extract and a highly purified enzyme preparation. Hypotaurine and methanesulfinic acid doubled sulfurtransferase activity in the partially purified extract at 30 mM, but inhibited the purified enzyme to 57% (hypotaurine) and 27% (methanesulfinic acid) of control activity at the same concentration. Pyruvate, phenylpyruvate, oxobutyrate, and oxoglutarate each inhibited the extract and purified forms of mercaptopyruvate sulfurtransferase. Phenylpyruvate was the most effective inhibitor, reducing activity to 0.2% of control values in the extract, and 11% of control values for purified MPST when added to the reaction at 30 mM. Other compounds tested (see Table 1) had a negligible effect on sulfurtransferase activity. A heat stable cofactor was found in boiled kidney extract which stimulated sulfurtransferase activity in the extract but inhibited sulfurtransferase activity in the purified enzyme, as was observed for hypotaurine and methanesulfinate. The boiled extract had no thiocyanate forming activity of its own. The cofactor operated in synergy with methanesulfinate, but independently of hypotaurine.
Oxygen concentration regulates EGF-induced proliferation and EGF-receptor down regulation.
Reducing oxygen from 20% to 2.5% increases EGF-induced DNA synthesis and cell proliferation in cultures of human diploid fibroblasts. Reducing oxygen also changes the pattern of EGF binding to the cell surface. The loss of surface binding that follows EGF attachment to cells in 20% oxygen does not occur in 2.5% oxygen.
Turnover of human and monkey plasma kininogens in rhesus monkeys.
The normal metabolic turnover of plasma kininogens was studied by measuring the disappearance of intravenously administered radiolabeled human and monkey plasma kininogens from the circulation of healthy adult rhesus monkeys. Curves obtained by plotting log radioactivity against time could be expressed as double exponential equations, with the first term representing diffusion, and the second, catabolism. No significant difference between the turnovers of human and monkey kininogens was observed. The difference between the t1/2 of high molecular weight kininogen (25.95 +/- 1.60 h) (mean +/- SEM) and that of low molecular weight kininogen (18.94 +/- 1.93 h) was only marginally significant (P less than 0.05). In contrast, a highly significant (P less than 0.001) difference in their mean catabolic rates (1.12 +/- 0.08 d-1 for high molecular weight kininogen vs. 2.07 +/- 0.09 d-1 for low molecular weight kininogen) was observed. These differences between the two kininogens were attributed to differences in their distribution between the intra- and extravascular pools. Studies of kininogen turnover will be useful in elucidating the in vivo functions of the various kininogens in health as well as during clinical illness.
Enterotoxic shock in rhesus monkeys. The role of selected bloodborne factors.
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Activation of the kallikrein-kinin system in Rocky Mountain spotted fever.
Activation of the kallikrein-kinin system, as indicated by increased plasma kallikrein and depleted plasma kininogen, prekallikrein, and kallikrein inhibitor, was observed in five patients with Rocky Mountain spotted fever. Four of the patients had petechial rashes characteristic of vasculitis. Three patients had alterations in coagulation consistent with disseminated intravascular coagulation, although no hemorrhagic syndrome was found. Our data, along with the known physiologic actions of kinins, suggest a possible role for the kallikrein-kinin system in the pathophysiology of vasculitis, disseminated intravascular coagulation, circulatory shock, and other complications of infection with Rickettsia rickettsii.
Model for disseminated intravascular coagulation: bacterial sepsis in rhesus monkeys.
DIC is a hemorrhagic syndrome frequently encountered as a complication in severe gram-negative bacterial sepsis. An animal model for sepsis-associated DIC was developed in order to permit study of the appearance and development of this syndrome in relation to the entire disease process. Rhesus monkeys (4 to 6 kg) were infected by intravenous injection of 10(9) Salmonella typhimurium organisms and studied for a period of 7 to 10 days following infection. Ten of 23 infected monkeys developed petechial rash characteristic of DIC, which appeared on days 1 to 2 infection and lasted 4 to 5 days. In the group of monkeys developing rash, activation of coagulation was suggested by an 80% decrease in platelet count and 20% to 30% increases in PT and APTT. Fibrinolytic system activation was indicated by the appearance of FDP. Kinin system activation was evidenced by decreases in both prekallikrein nad kininogen. Changes in laboratory tests suggestive of subclinical DIC were also noted in infected monkeys which did not develop a rash. Pathologic evidence of DIC was obtained through observation of numerous fibrin thrombi in the kidneys of the only monkey which died in the course of infection. Occurrence of DIC in association with this experimental infection in rhesus monkeys was established on the basis of clinical, laboratory, and pathologic criteria. Expression of the syndrome on days 1 to 2 following infection correlated with the period of increasing bacteremia.
Synthesis and secretion of alpha2-macroglobulin by cultured human fibroblasts.
The following observations indicate that cultured human WI-38 fibroblasts synthesize and secrete alpha2-macroglobulin into serum-free medium: (a) after incubation of cultures with [35S]L-methionine, a labeled protein appeared in the medium which was precipitated by antiserum directed against alpha2-macroglobulin; (b) after incubation of cultures with [35S]L-methionine, a major band of radioactivity detected by polyacrylamide gel electrophoresis of the proteins in medium co-migrated with alpha2-macroglobulin; and (c) the amount of alpha2-macroblobulin in the medium, estimated both functionally and immunologically, increased with time in normal but not not puromycin-treated cultures.