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A review of laboratory and clinical data is presented which supports a proposed endemic control mechanism designed to destroy the initiation of any localized abnormal growth of cells regardless of whether the cells are normal or aberrant. The emphasis of this article hypothesizes how the endemic control mechanism distinguishes between a fertilized ovum and fetus--which are also foreign to the mother's system--so that the fetus is not rejected by the endemic control mechanism that destroys other types of localized abnormal cell growth in the body. These data support a commonality between endemic control of pregnancy, tissue repair, and cancer growth and development.

An improved procedure is described for the recovery and purification of the coenzyme A-synthesizing protein complex (CoA-SPC) of Saccharomyces cerevisiae (bakers' yeast). The molecular mass of the CoA-SPC, determined prior to and following its purification, is estimated by Sephacryl S-300 size exclusion chromatography to be between 375,000-400,000. Two previously unreported catalytic activities attributed to CoA-SPC have been identified. One of these is CoA-hydrolase activity which catalyzes the hydrolysis of CoA to form 3',5'-ADP and 4'-phosphopantetheine, and the other is dephospho-CoA-pyrophosphorylase activity which catalyzes a reaction between 4'-phosphopantetheine and ATP to form dephospho-CoA. The dephospho-CoA then reacts with ATP, catalyzed by the dephospho-CoA-kinase, to reform CoA. This sequence of reactions, referred to as the CoA/4'-phosphopantetheine cycle, provides a mechanism by which the 4'-phosphopantetheine can be recycled to form CoA. Each turn of the cycle utilizes two mol of ATP and produces one mol of ADP, one mol of PPi, and one mol of 3',5'-ADP. Other than the hydrolysis of CoA by CoA-SPC, the 4'-phosphopantetheine for the cycle apparently could be supplied by alternate sources. One alternate source may be the conventional pathway of CoA biosynthesis. Intact CoA-SPC has been separated into two segments. One segment is designated apo-CoA-SPC and the other segment segment is referred to as the 10,000-15,000 M(r) subunit. The 5'-ADP-4'-pantothenic acid-synthetase, 5'-ADP-4'-pantothenylcysteine-synthetase, 5'-ADP-4'-pantothenylcysteine-decarboxylase, and CoA-hydrolase activities reside in the apo-CoA-SPC segment of CoA-SPC. Whereas the dephospho-CoA-kinase and the dephospho-CoA-pyrophosphorylase activities reside in the 10,000-15,000 M(r) subunit. Thus, the 10,000-15,000 M(r) subunit mimics the bifunctional enzyme complex that catalyzes the final two steps in the conventional pathway of CoA biosynthesis.

Subclinical infection is associated with preterm rupture of the membranes (PROM) and preterm labor (PTL) in many cases. It was hypothesized that antibiotic treatment might delay delivery and/or decrease infectious morbidity in those with PROM or PTL. Patients from 19 to 34 weeks with PROM and no labor or PTL with intact membranes (but not both) were separately randomized to receive ampicillin versus placebo in addition to usual therapy. There were 36 women with PTL (21 ampicillin/15 placebo) and 84 with preterm PROM (41 ampicillin/43 placebo). Demographically, the treatment and placebo groups were similar. Outcome variables analyzed included delivery delay after treatment, maternal chorioamnionitis/endometritis, Apgar score, neonatal infection, or respiratory distress, and hospital stay. There were no significant differences between the ampicillin and placebo groups in those with PTL or preterm PROM as it concerned outcome parameters. Adjunctive ampicillin used for treatment of idiopathic PTL or preterm PROM was not beneficial in this study.

Meperidine and its principle metabolite, normeperidine, were given intravenously to four non-human primates prior to cesarean delivery in an equivalent dose for human parturients. The status of the infants regarding neonatal depression was assessed at delivery. Repeated blood samples from both the mother and the neonate were obtained over a period of 4 days. The levels of meperidine and normeperidine were analyzed. The results showed that the metabolism of meperidine and normeperidine in the non-human primate was essentially the same as that observed in the human parturient. In addition, normeperidine appeared to be more toxic than meperidine to the neonate. Finally, there does not appear to be an evidence for neonatal metabolism of meperidine to normeperidine.

During a one-year period, 838 nonstress tests, 425 nipple stimulation contraction stress tests (NS-CSTs), and 115 spontaneous CSTs were done. Results were compared to those of NSTs and CSTs done by classic methods during a previous one-year period. The results revealed no hyperstimulation from contraction stress testing with nipple stimulation, and a significant reduction in the time to perform both tests conducted simultaneously when compared to the nonstress test plus classic oxytocin challenge test. The time to perform the combined tests compared to the routine nonstress test was not significantly different. Moreover, a cost-saving was also demonstrated. The combination of the NST and nipple stimulation CST appeared to be safe, efficacious, and cost-effective.

Hydrocortisone or placebo was administered to 126 women at risk for premature delivery who had immature lecithin:sphingomyelin (L:S) ratios in order to induce early surfactant synthesis. In 70 subjects (37 steroid-treated patients, 33 controls), L:S ratio was determined a second time between 9 hours and 7 days after therapy had been initiated. The treatment group showed a significant increase in the L:S ratio when compared to those who received the placebo. Moreover, patients who had fetomaternal disorders that accelerated or delayed lecithin production were also found to have increased L:S ratios after treatment. Fewer newborns developed respiratory distress syndrome (RDS) in the treatment group than in the control group and those in the former category who were affected by RDS had a milder clinical course.

The coenzyme A-synthesizing protein complex (CoA-SPC) is a multienzyme complex of Saccharomyces cerevisiae (Bakers' yeast), which has a molecular weight in excess of 200,000 as determined by Sephadex G-200 column chromatography. This multienzyme complex, which is insoluble in the crude yeast cell lysate, has been purified 229-fold. A cellular component of the yeast cell lysate, referred to as t-Factor, with a molecular weight of 400-1000 and chloride ion are involved in the solubilization of CoA-SPC. The CoA-SPC requires L-cysteine, D-pantothenic acid and ATP as substrates. The terminal CoA-SPC-bound intermediate is dephospho-CoA, which is subsequently phosphorylated and released from the complex as CoA. The sequence of reactions for the synthesis of CoA by the CoA-SPC differs significantly from those previously proposed for other systems. It could be that the reaction sequence is unique for the yeast cell.

Evidence is presented which indicates that S-(1,2,3,4-tetrahydro-2-hydroxy-1-naphthyl)-L-cysteine (THN-cysteine), formed by the reaction of 1,2-epoxy-THN with cysteine, can be incorporated into protein; The position of incorporation of THN-cysteine into protein would depend on whether the epoxide of THN reacts with cysteinyl-tRNACyS or with cysteine. In both cases, the mechanism of incorporation of THN-cysteine into protein is the same as for the natural amino acids. For example, the incorporation of THN-cysteinyl-tRNACyS is stimulated by Poly-UG, the code for tRNACyS, and would be expected to be substituted for cysteine in protein being synthesized, whereas THN-cysteine not previously esterified to tRNA is activated by the isoleucyl- and valyl-RNA synthetases, and its incorporation is stimulated by Poly-AU and Poly-UG, respectively. Consequently, in this case, THN-cysteine would substitute for isoleucine and valine during protein synthesis.

Previous data have suggested that the B-protein assay might prove to be useful in the assessment of patients with cancer after various therapeutic modalities. The assay's effectiveness was evaluated by prospective study of 133 patients with cervical, uterine, or ovarian cancer. After therapy, B-protein levels remained elevated in 17 nonresponding patients who eventually died of the disease. In contrast, 88 patients experienced a significant reduction in B-protein levels measured 90 days after treatment. Among this group, 25 patients demonstrated elevated B-protein levels during the 2-year follow-up period and all were confirmed to have persistent or recurrent disease. These data indicate that monitoring serum B-protein levels can be beneficial in the posttherapeutic management of gynecologic malignancies.

Pregnancy in patients with sickle cell disease has been a significant threat to maternal survival and good reproductive outcome. In the past several years, statistics for both maternal and perinatal outcome have improved. There is controversy, however, as to whether this improvement has resulted from the use of maternal transfusions or the aggressive and intense medical management afforded these patients in recent years. This study details the reproductive experience of 80 pregnant patients with significant hemoglobinopathies, 75 of whom were treated with partial prophylactic exchange transfusions during gestation. Each of the 75 patients who completed the protocol received 2 transfusions using buffy coat-poor washed packed red cells. The results show that there was no maternal mortality and a significant improvement in maternal morbidity compared to previous studies. There was also a significant improvement in fetal salvage, with a perinatal mortality rate of 26 per 1000. In addition, there were fewer premature and low birth weight infants as compared to other studies in the literature. Although these results were favorable, only a randomized multicentered study in the future will detail advantages and disadvantages of such therapy in the gravid sickle cell patient compared to intensive medical treatment without transfusion.

Isoacceptor species of certain amino acid-specific transfer ribonucleic acids (tRNAs) were fractionated by gel permeation chromatography using Sephadex G-100. The separation is attributed to the 20% ethanol-1% NaCl solvent and to the characteristics of Sephadex. Isoacceptor tRNAs specific for cysteine, arginine, phenylalanine, and histidine were recovered from commercial tRNA of yeast by this method. Highly purified cysteine-specific tRNA, obtained by a method which would not be expected to separate isoacceptor molecules when fractionated by this procedure, was shown to contain two cysteine isoacceptor tRNAs.

Although meperidine appears to be the safest obstetric analgesic agent, it has been associated with infant respiratory depression in certain situations. It would appear that the incidence of fetal depression related to meperidine is dependent on the time of injection prior to delivery, the quantity of drug administered, and the rate of maternal metabolism of the analgesic. Previous work showed that meperidine is metabolized in the maternal system by one of three patterns. The present study demonstrates that the particular maternal serum pattern is characteristic for the individual, regardless of whether the patient is pregnant or not, and that the fetal depression, although usually mild, can be correlated with fetal pH data as well as Apgar scores. In addition, this study supports indirectly the contention that metabolites of meperidine rather than the parent compound cause fetal depression. It would appear, therefore, that in certain obstetric cases with a higher probability for infant depression, other analgesic agents might be considered, especially if the serum pattern indicates meperidine is being metabolized.

The disposition of meperidine was studied in 11 term pregnant humans after the administration of a single 50 mg intravenous dose of meperidine through 48 h post-injection. Half-lives of the rapid and terminal elimination phases were calculated as 2.3 and 13.3 h, respectively. These values are much greater than previously reported half-lives which were based on data collected over less than 8 h after injection. An accurate value for t1/2 beta may be particularly important in sequential dosing of analgesic medication. These pharmacokinetic constants calculated on data collected through 48 h in this study may have important clinical correlates.

This single-dose, double-blind, randomized, placebo-controlled study assessed the efficacy and safety of 50 mg of flurbiprofen (Ansaid, Upjohn) in the relief of postoperative pain following cesarean section, as well as vaginal or abdominal hysterectomies. Results show that both 50 mg of oral flurbiprofen and 10 mg of intramuscular morphine sulfate were significantly superior to placebo in 161 patients with respect to pain intensity after medication, pain relief scores, need for additional analgesia, and overall clinical evaluation of pain relief. By two hours after treatment, there were no significant differences between morphine sulfate and flurbiprofen in terms of pain intensity or degree of pain relief. According to investigators' global evaluations of efficacy, both active treatments were statistically superior to placebo. The only adverse reaction occurred in the morphine treatment group. Flurbiprofen administered orally for the relief of moderate to severe pain following major gynecologic surgery appears to be equal to morphine sulfate and superior to placebo in efficacy and safety. Unlike morphine, flurbiprofen is a nonparenteral, uncontrolled substance, and thus patient acceptance is improved while nursing time is decreased.

A reduction of morbidity and mortality rates in homozygous sickle-cell patients was found in those with high fetal hemoglobin (HbF) levels. This factor would lead one to believe that an adequate amount of this substance would be protective to a patient with this hemoglobinopathy. This study utilizing pregnant and nongravid females, as well as males, followed for long periods of time indicates that the HbF level fluctuates with crisis. Some patients had low HbF levels with many crises and others had high amounts of HbF with no crises. However, many patients with high levels on one occasion demonstrated a decrease in HbF levels when crisis occurred. More importantly, no patient had high levels of HbF during a crisis although the amount was elevated before and after the episodes. The possible explanation and ramifications of this finding are discussed.

In this study, 500 mg. of hydrocortisone were injected intravenously into 126 women every 12 hours for four doses in a double-blind, randomized fashion. These 126 subjects were at risk for delivery of a premature infant because of premature labor of fetomaternal disease necessitating intervention. There were 67 patients in the treatment group and 59 in the placebo group. All patients had immature lecithin/sphingomyelin ratios and/or were at less than 34 weeks' gestation. From these data, it appeared that there was a significant decrease in respiratory distress syndrome when the treatment group was compared to the placebo group. The neonatal survival rates also were improved significantly by steroid treatment. There was no demonstrable adverse steroid effect in mothers of fetuses in the long-term or short-term follow-up period, although a significant number of patients were lost to follow-up and the methodology of infant evaluation was imprecise. It would appear from these data that the injection of steroids is beneficial in mothers at risk of being delivered of premature infants. However, many questions remain to be answered before this method can be relied upon as therapy for women with premature labor.

Sickle cell anemia and other severe sickle cell disorders (hemoglobin SC and hemoglobin S-thalassemia) are known to complicate surgical procedures in susceptible patients. Although transfusions have been used preoperatively to increase the packed cell volume, we have recently used the method of partial exchange transfusion in the treatment of patients with these disorders in the preoperative period. Forty-two patients with significant sickle cell hemoglobinopathies underwent operative procedures on various surgical services. The goal was to obtain a hemoglobin A percentage of 40 or above in each case, and this required 480 to 1,150 c.c. of buffy coat poor washed red cells (mean 820 c.c.). The number of complications in the intraoperative and postoperative period in this study was compared to those found in the literature. There was a significant decrease in morbidity and mortality rates noted with the use of these transfusions. There appeared to be a great advantage on a cost-benefit ratio, as well as an improvement in the physiologic state of the patient. Although the results of this study show significant improvement over previous investigations, there are many facets unknown concerning the use of this modality under these and other conditions. Therefore, further investigation of this method and restriction of the method of Level III referral centers is advocated until enough patients have been studied to assess the long- and short-term complications of the procedure.

Characteristic alterations of enzymatic reaction rates by irradiation of the crystalline substrates for fixed periods with an Hg vapor lamp were reported by Comorosan in 1969. Results of single- and double-blind studies reported here support the validity of the key features of this striking and potentially important phenomenon.

The consistency of results using Nile blue staining of fetal cells in amniotic fluid to estimate fetal maturity has been demonstrated. Recently, evidence to support this method has been published from this laboratory. Several biochemical and technical factors were cited as important to the success of the method. This report deals with further testing of several Nile blue dyes (hydrochloride and sulfate) necessitated by changes in production and federal regulation of this compound. The results show Nile blue hydrochloride (HCl) to be the most superior dye regardless of color index. Buffered solutions (6.6) of Nile blue A (sulfate) improve its performance, but not to levels demonstrated by the HCl preparation. Storage at room temperature adversely affects each dye; however, the sulfate variety appears to be the most unreliable under these circumstances. For best results, it is recommended that Nile blue HCl be used and the solution (buffered or normal) be kept refrigerated.

The lecithin-sphingomyelin (L/S) ratio is acknowledged to be superior to most procedures for predictinf fetal lung maturity in normal pregnancy. In complicated gestations, however, errors have been reported. This study involves 686 normal gestations and 389 pregnancies complicated by fetomaternal diseases. The L/S ratio, creatinine level, and percent of fat-staining cells were measured in samples of amniotic fluid from these patients. The results showed good correlation of all three tests with fetal maturity as measured by weight, Dubowitz criteria, and incidence of respiratory distress syndrome in the normal patients. In the complicated pregnancies, however, the creatinine was unacceptable in up to 30% of the cases. The L/S ratio likewise decreased in accuracy for all parameters of fetal maturity measured. The Nile blue staining of the fetal cells appeared to be the most consistent technic in these cases. A fetal maturity battery comprised of these three assays and other methods of assessing fetal health is advocated in pregnancies complicated by certain disease states.

B-Protein, present in the serum of individuals with cancer, has been purified to electrophoretic homogeneity. The purification procedure consisted of chromatography on Sephacryl S-200, Affi-Gel Blue, Con A--Sepharose 4B, wheat germ lectin--Sepharose and preparative polyacrylamide gel electrophoresis. The molecular weight of B-Protein is estimated to be 100 000 to 120 000. It is a glycoprotein which appears to be composed of two subunits, each with a molecular weight of approximately 52 000. Analytical polyacrylamide gel electrophoresis and analytical ultracentrifugation data indicate that purified B-Protein is homogeneous. Isoelectric focusing studies also show the purified B-Protein to be homogeneous in composition consisting of a single band of pI = 4.8. Amino acid analysis is consistent with this acidic isoelectric point. Other analyses indicate that B-Protein contains 7% carbohydrate and 7% lipid in the form of triglycerides.

The coenzymes A-synthesizing protein complex (CoA-SPC) of Bakers' yeast synthesizes coenzyme A in an in vitro system from the precursors ATP, D-pantothenic acid and L-cysteine. CoA-SPC has been produced on a small scale by freezing Bakers' yeast cells in a mixture of diethyl ether and solid CO2, followed by a thawing period, and subsequent removal of the diethyl ether by vacuum. The resulting yeast lysate was then stirred for 18 h in the presence of t-Factor to solubilize CoA-SPC. When a greater quantity of CoA-SPC was needed, the danger associated with the use of a large volume of diethyl ether was apparent. Therefore, the freezing step involving diethyl ether and solid CO2 has been replaced by a process of slowly drying fresh Bakers' yeast until approximately 34% of the initial weight of the yeast remained as dry solids. The yeast solids were ground to further disrupt the cell wall and membrane structure. The grinding step was followed by rehydration of the dry yeast solids with deionized H2O and stirring the rehydrated yeast for 18 h to solubilize CoA-SPC.

External cephalic version with tocolysis at or near term has been advocated to avoid cesarean birth for breech presentation. In our institution this maneuver was successfully performed in 207 of 304 parturients without major complications, and all but six had vertex presentation at delivery. The success of version was inversely correlated with gestational age but was not correlated with ease of version, number of attempts, or placental location. When this 3-year period was compared with the previous three years (1979 to 1981), there was a significant reduction in the number of breech presentations during labor, whereas the total delivery rate remained relatively constant over the 6-year period. It appears that in a carefully selected population, external version near term can be used safely to reduce the need for abdominal birth because of breech presentation.

In this study the immediate neonatal acid-base status, obtained via a double-clamped segment of umbilical cord, in 75 term, singleton vaginal deliveries was compared to electronic fetal heart rate recordings and Apgar scores. Of 75 neonates, 59 had 1-minute Apgar scores greater than or equal to 7 and 52 had an initial pH greater than 7.20. Six of the 16 neonates with a 1-minute Apgar score less than 7 demonstrated a low pH (less than 7.20). At 5 minutes only eight of 75 neonates had Apgar scores less than 7 with six of the eight having pH values less than 7.20. Of those neonates with Apgar scores greater than or equal to 7 and pH less than 7.20 (seven neonates at 1 minute, two at 5 minutes), none had metabolic acidosis. Eighteen fetal heart rate tracings were considered abnormal; acidosis was confirmed in eight (44%) by pH criteria, yet only three of the eight neonates had low Apgar scores. Our investigations suggest that the combination of fetal heart rate monitoring, cord blood pH, and Apgar assessment is better than any one parameter alone as an evaluation of fetal status just after delivery.

Previous work has shown that both meperidine and normeperidine are transferred across the placenta to the fetus. Little is known in primates, however, about the tissue deposition of these compounds. Four pregnant, dated rhesus monkeys within one week of term were anesthetized for cesarean delivery. An equal mixture of meperidine and normeperidine was administered as an intravenous bolus 10 minutes before delivery (1.25 mg/kg). The infants were then sacrificed at 20 minutes after birth and the concentration of the compounds in various organ systems were analyzed by gas-liquid chromatography and mass spectroscopy (GLC-MS). The infant serum 20 minutes after delivery revealed a meperidine concentration of 2.23 micrograms/ml and a normeperidine level of 0.67 micrograms/ml (3:1). In contrast, the tissues analyzed showed a much higher concentration of the metabolite in the liver (1:7), gallbladder (1:3), and brain (1:2). Other tissues, such as muscle and kidney, demonstrated equal levels of the two compounds. The authors conclude that normeperidine is quickly transferred to fetal tissues and to a greater degree than the parent compound in certain organs. The increased distribution, particularly in the brain, could account for the toxic actions in the cerebrum of the derivatives of meperidine.

Controversy exists concerning the positive correlation of maternal diabetes mellitus and the propensity for the progeny to develop respiratory distress syndrome (RDS). The increased incidence of RDS in these offspring seems to occur despite the various physical and biochemical assessments which indicate a mature lung profile. Recent data seem to incriminate insulin antagonism of normal fetal physiologic processes as the principal culprit. Strict control of maternal glucose metabolism in the pregnant diabetic may be essential in reducing RDS in the infant of a diabetic mother.

The efficacy of correlating the L/S ratio in the amniotic fluid with fetal lung maturity has been substantiated in normal pregnancies. In gestations complicated by fetomaternal diseases, however, the assay is less reliable. This study involves 555 pregnancies in which there was a significant maternal, fetal, or placental disorder. The L/S ratio was related to fetal respiratory maturity as measured by Dubowitz criteria and the occurrence of RDS. The results show that pre-eclampsia, chronic hypertension, diabetes (Class D, E, F), significant cardiovascular disease, severe hemoglobinopathies, various congenital anomalies, chronic placental insufficiency, and prolonged ruptured membranes accelerated the L/S ration. Conversely, mild diabetes (Class B, C), intrinsic renal disease, hepatitis, collagen disease, hydrops fetalis, syphilis, and toxoplasmosis were associated with a delay in the L/S ratio. A significant increase in erroneous responses was noted in these patients when the L/S ratio was correlated to infant maturity and to the incidence of RDS. Possible mechanisms for these findings are discussed.