Perinatal developmental changes in hepatic UDP-glucuronyltransferase.

Postnatal developmental changes in hapatic microsomal UDP-glucuronyltransferase were studied in the rat. The previously reported postnatal decline in the capacity of microsomal fractions to glucuronidate p-nitrophenol was found to be observable in unperturbed preparations only at non-saturating concentrations of the substrate UDP-glucuronic acid. At saturating concentrations of UDP-glucuronic acid, activity is identical in newborns and adults. Kinetic analysis revealed that the enzyme from liver of newborns has a much higher affinity for UDP-glucuronic acid than does the enzyme in adults, but the same activity at Vmax. On the other hand, the enzyme from adult liver microsomal fractions can be activated by the physiological allosteric effector UDP-N-acetylglucosamine, whereas the enzyme from newborns is largely unaffected by it. Thus it appears that the number of enzyme active sites is not changing; rather, the enzyme is maturing to a more highly regulable form. There were also differences between the enzymes in newborns and adults in their response to perturbation of the membrane-lipid environment by detergent and phospholipase A. Possible interpretations of these differences are discussed.     

Study of symptoms in middle life with special reference to the menopause.

In an attempt to clarify the nature of the "menopausal syndrome" a survey of symptoms was carried out by means of postal questionnaires in a population sample of 1120 women and 510 men. Special care was taken to avoid letting the participants know that the survey was mainly concerned with the menopause. Response rates were 72% for women and 68% for men. Analysis of patterns of symptoms by age and sex showed that peaks of prevalence of flushing and sweating were closely associated with the mean age of menopause, coinciding with it or occurring a little after it. Less impressive peaks of prevalence of a group of minor mental symptoms were associated with an age just preceding the mean age of menopause. Complaints about aching breasts, irritability, and low backache diminished after the menopause. No association with the menopause was found for various other symptoms. The results of this study support the view that the menopausal syndrome exists but do not, of course, provide any evidence concerning the effectiveness (or safety) of hormone treatment.     

Epidemiology and clinical significance of cervical erosion in women attending a family planning clinic.

Women attending a family planning clinic were studied to determine the relation between cervical erosion and clinical and social characteristics. The appearance of the cervix was recorded without knowledge of the women''s symptoms. The prevalence of erosion increased with parity but, when the effects of other factors were controlled, decreased in women aged 35 and over. Erosion was significantly more common in women taking the "pill" and less common in women using barrier methods of contraception than in others. There was considerable variation between doctors in the reporting of erosion. No association was found between erosion and postcoital bleeding, dyspareunia, backache, or dysuria. There was a significant but modest association between erosion and vaginal discharge and a suggestion that erosion may sometimes be associated with nocturia and frequency of micturition. Vaginal flora was similar in women with and without erosion. Cervical erosion should not be regarded as pathological in asymptomatic women, nor should it be assumed necessarily to be the cause of symptoms in women with genitourinary complaints.     

A rapid radioassay for sphingosine kinase

A solvent-extraction-based radioassay for measuring sphingosine kinase (SKase) activity has been developed. The assay utilizes [3H]sphingosine substrate and differentially extracts the [3H]sphingosine-1-phosphate product. The extracted radioactivity is demonstrated to be primarily [3H]sphingosine-1-phosphate with less than 1% contamination by [3H]sphingosine. When assaying SKase activity in the soluble cell fraction, the extraction efficiency of the labeled sphingosine-1-phosphate product is a reproducible 78%, which allows for a simple back calculation to correct for the 22% extraction loss. With minor modification, the assay is also a reproducible procedure for determining SKase activity in subcellular membrane fractions. The assay is far more rapid than thin-layer chromatography and high-performance liquid chromatography methods, which makes it possible to do a large number of assays in a short period of time. The utility of the assay is demonstrated by using it to conduct a complete bisubstrate kinetic analysis of rat heart SKase.     

Investigation of Relation between Use of Oral Contraceptives and Thromboembolic Disease. A Further Report

The results of a previous study of the use of oral contraceptives by married women discharged from hospital with a diagnosis of thromboembolic disease in the years 1964–6 were reported by us last year. The present paper adds results relating to patients discharged during 1967 and a few data, that could not be sought previously, for patients discharged with cerebral or coronary thrombosis from three of the hospitals in the earlier period.Of 84 patients with deep-vein thrombosis or pulmonary embolism 42 (50%) had used oral contraceptives during the month preceding the onset of their illness, while only 23 of the 168 controls (14%) had done so. No differences in risk were found either for the types of preparation or for the duration of use. After allowance for age and height, the patients with venous thromboembolism were about 10 lb. (4,535 g.) heavier than the control patients, irrespective of whether they were using oral contraceptives or not. No appreciable difference was found between the smoking habits of patients with and without venous thromboembolism treated during 1967, nor between women who were using oral contraceptives and those who were not. The trend in hospital admissions for venous thromboembolism with time corresponded to the trend in the use of oral contraceptives, and there was no evidence to suggest that the number of admissions was affected by publicity about the risk of using the preparations. Of 19 patients with cerebral thrombosis 11 (58%) had been using oral contraceptives, compared with an expected figure of 3.5 from the experience of the control subjects. All the published data (clinical, angiographic, and post-mortem) show that the thrombosis affects the cerebral arteries rather than the cerebral veins. Of 17 patients with coronary thrombosis 2 (12%) had been using oral contraceptives, compared with an expected figure of 2.1. The patients with coronary thrombosis smoked more than the control patients and were, on average, 8.3 lb. (3,765 g.) heavier than control women of the same age and height.The new evidence strengthens the belief that oral contraceptives are a cause of venous thromboembolism and cerebral thrombosis but does not indicate that they are a cause of coronary thrombosis.     

Dominance Rank and Parental Investment in Swine (Sus scrofa domesticus)

Using domestic swine, we tested the general prediction from life history theory that females increase their investment in offspring with increasing age and parity. Because increased investment may have a greater beneficial impact on the lifetime reproduction of sons than daughters, we also tested the prediction that older females would invest more in sons than in daughters compared to younger females. Finally, we examined whether age- or parity-related patterns of change in reproductive effort were associated with differences in the social dominance ranks of females. Female swine from a large number of domestic breeds were assigned to social groups, and their dominance ranks were determined based on the outcome of agonistic encounters. The prediction that older females produce larger litters was supported, but the increase was related only to age, not to parity. Across all ages, high-ranking females produced a greater proportion of sons than low-ranking females. Contrary to our prediction, there was no rank-related change in the proportion of sons born with increasing age or parity. However, the mean body masses offspring born to high-ranking females increased with increasing maternal age and parity, but this was not the case for offspring of low-ranking females. Studies of free-ranging groups of swine are needed to determine whether an increase in body mass at birth would have different effects on the reproduction of sons or daughters.     

Measurement of nitrogenase activity in legume root nodules: In defense of the acetylene reduction assay

The closed acetylene reduction assay has been used as a measure of nitrogenase activity and an indicator of N₂ fixation in Rhizobium/legume symbioses for 25 years. However, starting 10 years ago this assay has come under harsh criticism as being inaccurate. Currently, confusion exists regarding the conditions under which the acetylene reduction assay can be used accurately, or whether it can be used at all as a measure of nitrogenase activity. This article reviews the circumstance that has lead to this confusion. The author argues that under the proper assay conditions and with the appropriate checks, the closed acetylene reduction assay is still a valuable tool in assessing relative differences in nitrogenase activity in Rhizobium/legume symbioses.     

Factors affecting social behavior and reproductive success of male rhesus monkeys

This paper reviews aspects of life history that influence the reproductive success of male rhesus monkeys. Recent theories propose that there is some optimum level of inbreeding for each population and that behaviors related to group transfer by males are the result of selection pressure toward such an optimum. Group changing by males is clearly linked to the effects of testosterone at sexual maturation. A male’s maternal genealogical rank is not consistently related to the age at which it leaves the natal group, but social interactions within the natal group may influence the age of departure. Choice of the new group is influenced by the operational sex ratio and the presence of maternal relatives. Rank in the new group is positively correlated with seniority. Seniority, in turn, is influenced by the rank of the male’s natal group, his mother’s genealogical rank, and the presence of male siblings in the new group. Much of this effect is due to the high mortality of males born to females and/or groups of low rank. Most studies show a positive association between male reproductive success and rank. Males from high-ranking groups and/or maternal genealogies that join groups containing brothers tend to remain in those groups longer, attain a higher rank, and probably achieve higher levels of reproduction than other males.     

The effects of ions on the conjugation of xenobiotics by the aralkyl-CoA and arylacetyl-CoA N-acyltransferases from bovine liver mitochondria

The aralkyl-CoA:glycine N-acyltransferase and the arylacetyl-CoA:amino acid of N-acyltransferase were purified from bovine liver mitochondria and their response to a variety of ions investigated. The activity of the aralkyl transferase was inhibited by divalent cations with all substrates investigated. For benzoyl-coenzyme A (CoA), K+ was a competitive inhibitor, competing for binding at the benzoyl-CoA binding site. With salicylyl-CoA, K+ did increase the dissociation constant (KD) for acyl-CoA but it was not a competitive inhibitor and in addition, K+ increased the Michaelis constant for glycine (Kglym) tenfold. The data suggest that the increase in Kglym is due to bound K+ forcing reorientation of salicylyl-CoA at the active site so that it impinges on the glycine binding site. Inorganic anions and cations did not affect the extent of product inhibition by hippuric acid with either acyl-CoA and this was because they affected the binding of acyl-CoA and hippuric acid to the same extent. Ions did, however, greatly reduce the extent of product inhibition by CoA. This is critical because under approximate in vivo conditions (2.5 mM CoA), the salt-free enzyme would be almost completely inhibited by CoA. The arylacetyl transferase was activated by inorganic ions when assayed at saturating substrate concentrations. However, at physiologic concentrations of glycine certain salts were modestly inhibitory. The inhibitory effect of KCl was characterized by a large decrease in the affinity of the enzyme for phenylacetyl-CoA, suggesting that the arylacetyl-CoA region of the active site contained an inhibitory ion binding site. At low (physiologic) concentrations of substrate, the arylacetyl transferase was extensively inhibited by CoA and this inhibition was greatly reduced by ions. The 3'-phosphate group on CoA was found to be important for binding to the salt-free enzyme but in the presence of ions its importance was diminished. In the absence of inorganic ions the affinity of the enzyme for phenylacetyl-CoA and naphthylacetyl-CoA was so high that it could not be measured. In the presence of KCl the KD values for phenylacetyl-CoA and naphthylacetyl-CoA were similar, but the Km for glycine was extremely high for 1-naphthylacetyl-CoA conjugation, which accounts for its slow rate of metabolism. Conjugation with glutamine had a high Michaelis constant for glutamine (KGlum) and a low maximum velocity (Vmax) which accounts for the absence of glutamine conjugation in vivo.