Sumner J. Yaffe's research while affiliated with National Institutes of Health and other places

Publications (128)

Chapter
An organism reaches maturity after successfully completing a continuous series of intricate and interlocking events. The developmental program is initiated at conception, and the processes of growth and development unravel a sequence that is predictable, although not completely understood. The sequence is associated with wide variations in physiolo...
Article
The disposition of theophylline was examined in seven children with asthma on two occasions before and on one occasion after chronic phenobarbital dosing (2 mg/kg/day). There was little intrapatient variability in apparent theophylline clearance between the two baseline assessments (0.081 versus 0.073 L/hr/kg). After 19 days of phenobarbital therap...
Chapter
Phototherapy for the treatment and prevention of neonatal infant jaundice is widely practiced. The effectiveness of photo-therapy in reducing hyperbilirubinemia in jaundiced infants is very well established,1’2 however, its widespread use has raised some doubts and concerns about its safety.3 Although, the short-term effects of phototherapy for the...
Article
The elimination pharmacokinetics of tobramycin sulfate was studied in 25 newborn infants of birth weight 0.7 to 4.7 kg during 31 treatment episodes. The peak serum concentrations after a 2.5 mg/kg dose were usually within the therapeutic range of 5 to 10 micrograms/ml; however, the serum predose trough values were elevated above the theoretical saf...
Article
Epidemiologic studies have provided much of the knowledge concerning adverse side effects of exposure to drugs and other xenobiotics transmitted via breast milk. Adverse effects can be immediate and usually recognizable or long-term and difficult to define. Acute effects may be due to individual idiosyncrasy, allergic reaction, or manifestation of...
Article
The effects of the combination of low protein diet feeding and endotoxin (E. coli, serotype 026 B6) upon rat hepatic microsomal mixed function oxidase (MFO) enzymes were investigated. Short-term (7 days) feeding of low protein (8%) diet and acute (single dose) exposure to endotoxin resulted in an additive decrease in MFO enzymes. However, chronic (...
Article
Pregnant rats were fed high-fat (HF, 35% calories) or low-fat (LF, 5% calories) diet from 18 days of gestation to the end of the suckling period. Thereafter, male progeny were fed stock diet for 6 months, then sacrificed or challenged for 3 days with HF diet. There were no immediate posttreatment effects at 30 days of age on liver microsomal cytoch...
Article
The effect of intrauterine malnutrition in rats on in vivo and in vitro drug metabolism at weaning was investigated. We have employed two experimental designs to produce intrauterine malnutrition, maternal dietary protein depletion starting at day 7 of gestation and unilateral ligation of the uterine artery on day 17 of gestation. At birth cross-fo...
Article
Young male rats (SD, CD strain) were fed semisynthetic isocaloric diets ad lib for different time periods (3,7,14, or 28 days); both carbohydrate (starch or sucrose) content and fat content were varied. High starch (HST) diet contained starch (73% of calories), corn oil (6%), and casein (21%); low starch (LST) diet contained 6, 73, and 21% of calor...
Article
This article reviews the delayed effects of anticonvulsants (phenobarbital, phenytoin, and valproate) administered in utero upon the reproductive function in the offspring. Experimental data from the authors' laboratories are discussed in light of this context. Furthermore, comments are made emphasizing the gaps in our knowledge concerning the prob...
Article
Exposure of rats to phenobarbital during late prenatal development decreased the concentration of testosterone in plasma and the brain during the late fetal, early postnatal, pubertal, and adult periods, By decreasing the production of testosterone in the brain during the period of sexual differentiation, phenobarbital may lead to sexual dysfunctio...
Article
1. Bacterial endotoxin, a soluble lipopolysaccharide, has been studied to ascertain its effects in vivo and in vitro on the hepatic drug-metabolizing enzymes of adult male and female rats. 2. 24 h after a single 1 X 0 or 2 X 0 mg/kg i.p. dose of endotoxin, hexobarbital sleeping time was significantly increased in adult male rats. Significant inhibi...
Article
The possible mechanism of action of phenobarbital in prenatal female rats has been studied using different inhibitors of protein/DNA/RNA synthesis. Administration of phenobarbital (40 mg/kg/day) subcutaneously from day 17 to day 20 of pregnancy resulted in a delay of the onset of puberty, disorders of estrous cycle, infertility, and high estrogen l...
Article
An oral theophylline product was given to eight lean, normal subjects and eight obese subjects (four with asthma and four normals) in a single-dose study. The mean apparent volume of distribution (Vd) was 0.472 +/- 0.08 liters/kg for the lean group and 0.321 +/- 0.063 liters/kg for the obese group (P less than 0.001). When Vd wax expressed in liter...
Article
Phenobarbital (PB) (40 mg/kg/day) was administered to pregnant rats at 12 to 20, 14 to 20, and 17 to 20 days of gestation and female offspring were tested for the onset of puberty, estrous cycle pattern, and fertility. Another group of rats received PB (20 mg/kg/day) during the neonatal period (1 to 8 days). PB administration during both the pre- a...
Article
The newborn is particularly susceptible to bacterial infection because of its underdeveloped immune system. The newborn's inability to localize infection can also delay diagnosis by altering the manifestations of infection. Anti-microbial therapy is complicated, however, by the immaturity and rapid changes in metabolic and physiologic functions dur...
Article
Phenytoin, an anticonvulsant which is commonly used in the treatment of epilepsy, is teratogenic in humans and produces cleft palate in susceptible rodents. We therefore investigated the effects of a teratogenic dose (50 mg/kg,S.C.) of phenytoin in the susceptible Ajax (A/J) and the resistant C57BL6 (B6) inbred strains of mice during the critical p...
Article
In perfused livers from normal developing rats, rates of p-nitroanisole O-demethylation, nearly undetectable at 8 days of age, increased progressively to a maximum of 5.1 mumol of p-nitrophenol formed per gram of liver wet weight per hour by 20 days of age. However, by 30 days of age, the rate of p-nitrophenol formation decreased to 2.8 mumol/g/h,...
Article
Previously we reported that PB administration during late pregnancy caused defects in sexual maturation of female offspring (delayed vaginal opening, irregular cycle and infertility). To elucidate the mechanism of these effects, inhibitors of protein RNA and DNA synthesis were studied. Time pregnant rats (S-D,CD strain) 5 per group, were injected,...
Article
Acute starvation, particularly in children, is often encountered due to infections. This is frequently accompanied by fever and requires antipyretic therapy. Since acetaminophen is widely used under these circumstances, we determined its toxicity (LD50) in young (8 day old) and adult male mice (strain CD-1). Animals were deprived of food for 6 hour...
Article
• Antipyretics should be employed in the pediatric population whenever it is the clinical judgment of the attending physician that fever should be lowered. Aspirin and acetaminophen are equally effective as antipyretics. The efficacy and safety of these two most common antipyretic agents are examined, and various studies with these agents are criti...
Article
Although infrequently an antibiotic of first choice for neonates, chloramphenicol (CL) may be indicated in selected instances of infection caused by aminoglycoside-resistant enterobacteriaciae, anaerobes, and ampicillin-resistant Haemophilus influenzae. Use of CL in neonates has been limited since the recognition that vascular collapse may occur as...
Article
Specific 3H-diazepam binding was measured in adult mouse (strain, Crl=CD-1) brain after four days of an inductive dose of phenobarbital pretreatment (i.p.). Sexual dimorphism was observed in 3H-diazepam brain binding, female mice had significantly higher benzodiazepine binding than males without any differences in apparent affinity constants (KD)....
Article
The frequency of gram-negative infections and endotoxemia in the perinatal period prompted an investigation of the effects of endotoxin (Escherichia coli 026B6) on hepatic drug metabolism. Gravid female rats given injections IP with different dosages of lipopolysaccharide during late pregnancy resulted in significant depression of the liver microso...
Article
Phenobarbital administration to pregnant rats from day 12 to day 19 of gestation suppressed body weight gain and produced significant effects on reproductive function in their offspring. These effects included delays in the onset of puberty, disorders in the estrous cycle, and infertility. Moreover, the animals exposed to phenobarbital in utero sho...
Article
The pharmacokinetics of two unmatched populations of asthmatic children, one from an asthmatic convalescent center in Denver and the other from an urban outpatient clinic, are compared after single and repeated dosing of a new asthma formulation, oxtriphylline syrup. Significant differences (p less than 0.05) in populations' theophylline total body...
Article
The effect of prenatal exposure to phenobarbital (40mg/Kg/day from day 12 to day 19 of pregnancy) on sexual development of male offspring was investigated. Anogenital distance of the male offspring exposed to phenobarbital was significantly smaller. Testicular descent was delayed by 1-3 days, but the age of onset of puberty did not change. Fertilit...
Article
The labeled dosage schedule that has long been on pediatric aspirin preparations is at variance with the recommendation in authoritative medical references, studies demonstrating antipyretic effectiveness in children, and the prescribing habits of pediatricians as revealed by a poll conducted by the authors. Aspirin pharmacokinetics are influenced...
Article
The pharmacokinetics of theophylline were investigated in 13 infants, 4 to 18 months of age. An inverse relationship was found between theophylline half-life and age. Volume of distribution did not differ from that reported by other authors in similarly aged infants. Our data suggest that childhood clearance rates of elimination can be achieved by...
Article
The frequency of gram negative infections and endotoxemia in the perinatal period prompted an investigation of the effects of endotoxin (E. coli. 026B6) on hepatic drug metabolism. Chronic dosing of endotoxin (0.2 mg/kg/d × 7 days) to lactating mothers significantly stimulated hepatic microsomal cytochrome P-450 (118%) and aminopyrine demethylase a...
Article
Major features included in the fetal trimethadione (3,5,5-trimethyloxazolidine-2,4-dione) syndrome are developmental delay, speech difficulty, V-shaped eyebrows, epicanthus, low set ears with anteriorly folded helix, palatal anomaly, and irregular teeth. Some patients also have intrauterine growth retardation, short stature, microcephaly, cardiac a...
Chapter
An organism reaches maturity only after successfully completing a continuous series of intricate and interlocking events. The sequence begins at conception, and the processes of growth and development advance in predictable fashion. The sequence is also associated with a wide variation in physiologic functions, many of which vary in proportion to b...
Article
The disposition of methicillin in normal subjects and in subjects with cystic fibrosis (CF) was studied after administration of single intravenous doses of 15 mg/kg. The area under the serum concentration vs. time curve for CF patients was, on the average, only 75% of that found for normal subjects. The low concentrations in serum were caused by mo...
Article
Persistent colonization of the respiratory tract with μs. aerug. is a major problem in children with cystic fibrosis (CF). Because gentamicin penetration of CF sputum is inadequate after parenteral administration, we undertook an investigation of the safety and efficacy of gentamicin aerosol. Nine CF children (5F, 4M) ages 6-15 years with moderatel...
Article
Infections due to pram-negative bacteria have assumed ever-increasing importance during the past several years. Endotoxin, a soluble lipopolysaccharide cell wall constituent of gram negative bacteria, is released into body fluids during infection by these organisms. A key aspect in the therapeutic management of patients with endotoxemia is the admi...
Article
GENETICALLY different inbred strains of mice have different susceptibilities to the production of cleft palate by a standard dose regimen of corticoids at the critical period during palatal organogenesis1. Because in target tissues corticoids form a specific cytoplasmic cortisol-receptor complex which interacts with the genome, resulting in activat...
Article
Benzo(a)pyrene hydroxylase activity was found in the bone marrow of control and 3MC-induced New Zealand white rabbits. This activity was localized in the microsomal fraction, was NADPH dependent and CO sensitive. The reaction was inhibited by 7,8-benzoflavone indicating that it was mediated by the 3MC-inducible form of cytochrome P-450. BP hydroxyl...
Article
Extract: This report deals with quantitative and qualitative investigations of alkaline phosphatase in two unrelated infants with the severe infantile form of hypophosphatasia. Both affected infants had no detectable leukocyte alkaline phosphatase activities and both sets of parents and one sibling tended to have low but variable leukocyte enzyme a...
Article
The pharmacokinetics of gentamicin were examined on two occasions using intravenous and intraperitoneal routes in five children undergoing intermittent peritoneal dialysis for chronic renal failure. Serum, urine and dialysis fluid (DF) were assayed microbiologically for gentamicin and the data were subjected to computer analysis using equations evo...
Article
Rat livers were homogenized and microsomes were prepared by differential centrifugation. The livers of saline treated rats showed no histologic evidence of necrosis fat, or inflammation. On the other hand, the livers of E. coli endotoxin treated animals demonstrated limited changes consisting of hemorrhagic infarction, and some pericentral necrosis...
Article
Consent must be obtained prior to the institution of medical or surgical treatment. Pediatricians should keep informed concerning court decisions and statutes relative to consent and minors.
Article
Full-text available
Neonatal deaths from tracheal obstruction caused by congenital goiters have been reported from such widely scattered locales as Buffalo, New York, New York City, Philadelphia, Washington, D.C., Seattle, Tokyo, Japan, and Glasgow, Scotland. The mothers of these infants had asthma and were receiving conventional doses of iodides, either as potassium...
Article
During the last several years there has been continued pressure from consumers, legislators, and health administrators to mandate generic prescribing. It has been proposed that requiring physicians to prescribe by generic rather than brand name and allowing pharmacists to substitute generically equivalent drug products would save consumers millions...
Article
The Committee on Drugs unites with the Joint Committee on Physical Fitness, Recreation, and Sports Medicine in condemning the use of drugs to improve athletic performance, However, the Committee on Drugs would like to clearly distinguish between the promiscuous use of drugs and their pharmacologic use to control a specific disease state enabling th...
Article
Research on the fetus and newborn is of the greatest importance in contributing to the health and welfare of the entire population. Such research, motivated by humane concern, should be continued and fostered, subject to adequate and clearly defined safeguards.* The American Academy of Pediatrics recognizes that through research involving previable...
Article
The compliance with treatment of acute otitis media in 300 pediatric outpatients was evaluated. Complete compliance in taking prescribed antibiotics was noted in 7.3% of the patients. Pharmacists dispensed less than prescribed amounts of antibiotics to 15% of patients. Bottles were incorrectly labeled 3% of the time. Volumes of 130 "teaspoons" exam...
Article
Although pediatricians usually take great care in accurately calculating medication for their patients, the important processes of measuring and administering the dose are often overlooked. Many of the problems encountered in the administration of tablets and capsules to small children have been overcome by the production of medications in liquid f...
Article
The Committee on Drugs has reviewed the pharmacology of marihuana with special emphasis on effects in man because of the enormous impact of this drug on society. Much of modern day society's reaction to and attitudes about this psychoactive agent does not reflect its pharmacology, and it is only recently that pertinent biologic facts about marihuan...
Article
The first annual W. E. Upjohn Lecture concerned itself with the interrelationship between administration of drugs to the pregnant woman and fetal outcome. The epidemiology of drug intake (both prescribed and self-administered drugs) during pregnancy is reviewed, using data derived from several surveys conducted both in the United States and in Scot...
Article
Protein deficiency in post-suckling rats produced changes in the activity of hepatic drug-metabolizing enzymes. Significant decreases occurred in the N-demethylation of aminopyrine, in the azo-reduction of neoprontosil and in sulfokinase activity (using p-nitrophenylsulfate as SO4 donor). An increase was recorded for the glucuronidation of p-nitrop...
Article
The purpose of this investigation was to determine the relationship between dose and the distribution of salicylate in the body. The apparent volume of distribution was determined from the concentration of salicylate in plasma or serum at various times after salicylate ingestion and from the amount of drug remaining in the body at these times as as...
Article
Compliance with therapeutic regimens has been found to be very low in pediatric ambulatory patients. Physicians must recognize the extent of noncompliance among their patients and become aware of the factors contributing to it. Several practical measures can be taken to enhance compliance and thus ensure better health care.
Article
The apparent volume of distribution (Vd) of salicylate was determined in 11 children, 4 months to 16 years old, who had ingested from about 36 to over 340 mg of salicylic acid (mainly as aspirin) per kilogram of body weight. Vd was calculated from the amount of salicylate in the body at a given time (as determined by the amount of total salicylates...
Article
The halogenated hydroxyquinolines can cause serious, permanent neuropathy. Optic atrophy, causing permanent blindness, is the most commonly reported neuropathy in children. In young children, the onset of neuropathy is insidious and hard to diagnose. We, therefore, recommend that these drugs not be used in children, with two possible exceptions: th...
Article
Neutron activation analysis was employed to quantitate the levels of mercury (Hg) in human tissue and body fluids. Statistical analysis revealed:1.a. No significant differences (P > .05) in Hg levels among the members of each of the following groupings: (i) adult (15–91 years) and sub-adult (neonate through 14 years) frontal and cerebellar cortex,...
Article
Drug-protein interaction is of major importance in modulating drug distribution and action in the intact organism. Drug binding to serum proteins in the gravid female is of special interest because of physiological changes during pregnancy which may influence drug activity in the primary host and in the developing fetus. A detailed investigation of...
Article
The frequent episodes of peribronchial pneumonia seen in patients with cystic fibrosis require antibiotic administration often with anti-staphylococcal agents. Until now the data upon which to base dosage regimens have not been available. Serum dicloxacillin concentrations and urinary excretion rates were measured in 10 patients ranging in age from...
Article
Alcohol dehydrogenase activity in the supernatant fraction of liver homogenates was studied in adult and newborn mice. Newborn mice were found to have a lower specific activity than adult animals. Km values were higher in the new born animal. Electrophoresis showed two bands for the adult and only one for the newborn, with a greater intensity seen...
Article
The common problem of short stature in children who are growing at a normal rate is best managed by clarification of, and attention to, the psychological issues. This may require referral for expert psychological counseling. In a few instances, the physician, parents, and patient may agree that carefully supervised use of one of the synthetic will...
Article
The Committee on Drugs unites with the Joint Committee on Physical Fitness, Recreation, and Sports Medicine in condemning the use of drugs to improve athletic performance. However, the Committee on Drugs would like to clearly distinguish between the promiscuous use of drugs and their pharmacologic use to control a specific disease state enabling th...
Article
This article reviews the basic principles of teratology and discusses the handling of drugs during pregnancy in relation to the mother, placenta, fetus and neonate. Although the final response to a drug is due to complex interactions, the different components are discussed separately for the sake of clarity. A brief survey of different drugs curren...
Article
Bilirubin, dissolved in an aqueous KOH solution, was titrated with HCl in an automatic apparatus. Results indicate the bilirubin has two acid groups per mole of bilirubin. Varying concentration of bilirubin did not alter the pK′; increasing ionic strength produced a gradual decrease in pK′; and the effect of temperature on the pK′ also shows a rath...
Article
1. Development of the endoplasmic reticulum and its drug-oxidizing enzyme system was studied in perinatal rabbit liver and placenta from the 20th day of gestation to the 14th day of life. 2. The components of the microsomal drug-oxidizing electron transport chain and the drug-oxidizing capacity are absent, or present at negligible levels, in prenat...
Article
One of the most important concepts in pediatric pharmacology is that exposure to drugs or chemicals may have latent, unforeseen effects on the child later in life. Some of the most dramatic occurrences, other than teratogenesis, are those in which hormonal exposure during the fetal or newborn period alters adult sexual development. However, none of...
Article
Antihistamines were introduced in France by Halpern in 1942 and in the United States at the end of World War II; they had been investigated extensively during the war for therapy of motion sickness. By the late 1940s, a mass of information on the structure activity relationship had accumulated and most major drug manufacturens had introduced antihi...
Article
Full-text available
The abuse of amphetamines has become a problem of international significance. Japan was the first country to recognize this problem, and by 1954 there were an estimated 500,000 to 600,000 abusers in Japan. More than ten years ago Japan banned the use of amphetamines. The United Kingdom restricted distribution of amphetamines to hospital pharmacies...
Article
Anaphylaxis* is an acute reaction, which may range from mild self-limited symptoms to a grave medical emergency. It is caused by a variety of agents, usually occurs unexpectedly, frequently is iatrogenic, and can be fatal if not treated promptly and appropriately. Every physician's and dentist's office, pediatric outpatient clinic, hospital emergen...
Article
Activity of bilirubin glucuronyl transferase in mouse liver homogenates is low at birth, reaches a peak at 14 days of age, 2–3 times greater than adult values. Kinetic studies showed marked differences between microsomes derived from adult and 14-day-old animals. Michaelis-Menten constants (Km) were 5.9 × 10––5 m and 4 × 10––4 m respectively at the...
Article
In its broadest sense, drug interaction may refer not only to the reaction between two or more therapeutic agents, but also to the interplay between an administered agent and a component of the host. Thus we may have drug-drug and drug-food interactions, and drug interactions with a particular clinical condition. The latter is particularly true in...
Article
The frequent use of marijuana by American youth has compelled the Committee on Drugs to explore the present methods of and recommendations for controlling marijuana. On October 15, 1970, the Executive Board of the American Academy of Pediatrics endorsed in principle a statement on marijuana which was prepared by the Massachusetts Chapter of the Aca...
Article
Published reports and unpublished communications to the Committee on Drugs of the American Academy of Pediatrics indicate that substances potentially hazardous to the premature and full-term newborn infant continue to be used in the laundering of clothing, diapers, and bedding for hospital nurseries. In 1962 the Subcommittee on Accidental Poisoning...
Article
When broad-spectrum antibiotics were first introduced two decades ago for the treatment of acne, justification for such therapy seemed reasonably straightforward, e.g., the suppression of the suppurative inflammatory lesions commonly encountered in acne. As time went on, however, certain observations raised questions concerning the rationale for th...
Article
The plasma protein binding of diphenylhydantoin (DPH) in heparinized plasma from normal and hyperbilirubinemic newborn infants was investigated by means of an ultrafiltration technique utilizing 14C-DPH. At room temperature, pH 7.4, and with a plasma concentration of 16 μg of DPH per milliliter, the unbound fraction of DPH in cord plasma from 13 no...

Citations

... 115 While limited, the number of s t u d i e s i n v o l v i n g h u m a n s u b j e c t s i s i n c r e a sing. 98,[104][105][106][108][109][110]116 TCS and TCC as Endocrine Disruptors. An emerging additional toxic outcome of concern is endocrine disruption, 117 meaning an interfering of TCS and TCC with essential signaling systems in animals and humans, thereby adversely affecting development, sexual maturation, metabolism, and behavior. ...
... Thus, the rate of exposure has increased dramatically, even in the pediatric population. Historically, significant effects following unintentional pediatric marijuana ingestion were rare, and the relevant literature consists of single case reports and a small case series12345. In the United States, the decriminalization of medical marijuana has resulted in a significant increase in marijuana exposures in young children, and more severe symptoms can be observed, owing to the higher concentrations of marijuana in edible and medical products [6, 7]. ...
... In the literature, topical antihistamines produce mixed efficacy results, as reported in a recent review[50]. Furthermore, these agents are known to be sensitizers, which may further induce secondary allergic contact dermatitis after long-term usage of these agents[51]. Hence, we recommend against routine usage of these agents to manage EGFRIinduced pruritus. ...
... An effect on the neuro-endocrine axis, resulting in a lower progesterone level, is hypothesized to be a risk factor. This is supported by animal experiments [3]. It is plausible that this increase in prematurity is the female counterpart of the testicular dysgenesis syndrome and may be caused by endocrine disrupting chemicals (EDCs) (see below), or by direct effects of exogenous hormone-like substances such as phthalates during the pregnancy [4]. ...
... In all probability, the drug has an indirect effect on the development of different neurotransmitter systems in the rat brain. The drug metabolites may also be selectively toxic as the rate of metabolism and excretion of such a metabolite is liable to be delayed in the foetus [9]. It is also expected that HAL or its metabolites may remain in the maternal plasma concentration for extended period of time, thus affecting the CNS development. ...
... Also, for these experiments, we opted for a realistic human-equivalent dosage regimen consisting of 200 mg/kg three times daily. Since the half-life of APAP is likely <1-4 h in mice [62], this does not constitute continuous exposure as in our zebrafish experiments. Therefore, it is difficult to make direct comparisons between the effects of APAP in zebrafish and the results in the mouse model. ...
... Several authors have reported a relatively high renal clearance of 3-lactam antibiotics in patients with cystic fibrosis (Bergan & Michalsen, 1979; Jusko et al., 1974 Jusko et al., , 1975 Guggenbichler & Kienel, 1979; Yaffe et al., 1977; Spino et al., 1984). Various explanations have been offered including an increased tubular excretion. ...
... Only in lung, in which most feeble signals of NIS mRNA were detected, NIS mRNA was regulated in the opposite manner as that in the thyroid gland. Intriguingly, iodide has been used to thin mucus secretions in the respiratory tract as an expectorant drug for asthma or other pulmonary diseases [20]. It was also found that orally administered radio-iodide reaches bronchial lumen [21]. ...
... On the other side other hepatic conjugating systems such as N-acetyl-transferase have diminished activity during foetal life with no evidence that this might be an advantage or that maturation is substrate dependent (Weber & Cohen, 1968). There is some evidence that in this enzyme system (Weber & Cohen, 1968) as well as in glucuronyl transferase, maturation is connected with a switch from a foetal form of the enzyme to the adult one (Krasner & Yaffe, 1968). In any case the factors that bring about the maturation of the enzyme systems are not only of theoretical but also of immense practical interest as the speeding up of the maturation process constitutes the simplest solution to most of the therapeutic problems posed by neonatal hyperbili- rubinaemia. ...
... Different strains of mice respond with different frequencies of cleft palate to glucocorticoids. The level of glucocorticoid receptors in palatal cells correlates with cleft palate frequency in most mouse strains (38,39). ...