The metabolism of synthetic estrogens in non-users and users of oral contraceptives

Using both pulse injections and constant infusions of ³H-mestranol (³H-ME) (1) and ³H-ethinyl estradiol (³H-EE) we have studied the metabolism of these compounds in non-users and users of oral contraceptives. Following pulse injection of ³H-ME the disappearance of radioactivity could be described as a function which was the sum of two exponentials. Studied by both types of administration there was no difference in the metabolism of ³H-ME in the two groups; the overall mean ± SE metabolic clearance rate (MCR) was 690 ± 45 1/day/m², the mean ratio of the concentrations of radioactivity as EE following administration of ME (CR_BB^{M, E}) was 0. 23 ± 0. 02 and the mean [ρ]_BB^{M, E} (fraction of administered ME measured in blood as EE) was 0. 19 (95% confidence limits = 0.15 – 0. 23).Following pulse injection of ³H-EE the disappearance of radioactivity was best described as a function which is the sum of three exponentials. Results from both types of administration revealed no difference in the metabolism of ³H-EE between non-users. The overall mean ± SE MCR^EE was 630 ± 30 I/day/m². The MCR^EE is significantly (0. 02 > P > 0. 01) less than the mean MCR for estradiol reported previously, in both non-users and users of oral contraceptives. The use of oral contraceptives containing estrogens and progestins does not appear to influence the metabolism of the estrogen used. Approximately 20% of mestranol is converted to and appears in the blood as ethinyl estradiol.     

The location of the genes coding for hexon and fiber proteins in adenovirus DNA.

A serological analysis has been made of the capsid antigens hexon and fiber from 17 Ad5-Ad2+ND1 recombinants that enables us to determine the phenotype of the recombinants. By correlation of this data with the genetic and physical maps of the adenovirus genome, obtained by recombination and restriction endonuclease analysis, the genes coding for the hexon and fiber have been assigned to specific locations on the adenovirus DNA.     

Alkaline ribonuclease and ribonuclease inhibitor in mammary gland during the lactation cycle and in the R3230AC mammary tumour.

Alkaline RNAase (ribonuclease) and RNAase inhibitor were assayed to determine the potential role of the degradative process in regulating the amount of RNA in the mammary gland and mammary tumour. Very little free alkaline RNAase activity was found in the cytosol fraction of the mammary gland of virgin, pregnant, lactating or involuting Fischer rats. However, addition of p-chloromercuribenzoate to the assay medium revealed latent RNAase which, when expressed on a DNA basis, decreased during pregnancy and lactation. The cytosol latent RNAase is stable in 0.125 M-H2SO4. The non-cytosol RNAase activity also decreased during pregnancy and lactation. Addition of Triton X-100 produced slightly higher activity at all stages tested. The inhibitor activity in rat mammary gland was very low before pregnancy, increased gradually during pregnancy and more dramatically at parturition, continued to increase throughout lactation and returned to resting-gland values by the sixth day of involution. The increase during pregnancy may be due to the increased cellularity of the gland, whereas the gain during lactation was more than could be accounted for by increases in cell number. The R3230AC transplantable mammary tumour resembles the normal gland in early lactation with respect to both its cytosol and non-cytosol alkaline RNAase activities and its moderately high content of RNAase inhibitor. The relatively high inhibitor and low RNAase activities in both the gland of the lactating rat and in the tumour are of potential significance in maintaining high amounts of RNA and increased rates of protein synthesis in these tissues.     

Purification of the Thy-1 molecule from rat brain.

The present paper describes the characterization of the Thy-1 molecule from rat brain. The molecule was recognized by its antigens, which could be solubilized from brain membrane with deoxycholate. In the solubilized form the Thy-1 antigens were associated with a homogenous component with the following hydrodynamic properties: s20,w=2.2s,v=0.72ml/g and Stokes radius=3.0nm. The mol.wt. of the deoxycholateantigen complex was estimated to be 27000; these values are not significantly different from those obtained thymocyte Thy-1. Brain Thy-1 was further purified by affinity chromatography with lentil lectin coupled to Sepharose 4B, and more than 80% of the antigen was bound. The material eluted with methyl alpha-D-glucopyranoside was then filtered on a column of Sephadex G-200, and only one glycoprotein was found in the antigenically active fraction. On sodium dodecyl sulphate-polyacrylamide-gel electrophoresis the glycoprotein was very similar to the Thy-1 from thymocytes that binds to lentil lectin. Its apparent mol.wt. on 12.5% acrylamide gels was 24000, and it electrophoresed as a symmetrical band. Brain Thy-1 was antigenically indistinguishable from thymocyte Thy-1 when analysed with rabbit antisera raised against brain or thymocyte Thy-1.     

The clearing-factor lipase activity of isolated fat-cells.

1. When fat-cells are isolated from the epididymal adipose tissue of 24h-starved rats and incubated at 25 degrees C in the presence of dialysed serum, glucose, insulin, amino acids and heparin, the total clearing-factor lipase acitivity of the incubation system increases progressively over a period of several hours. 2. All of the increase in activity is accounted for by the appearance of enzyme in the appearance of enzyme in the incubation medium and the fat-cell activity does not change significantly. Cycloheximids, at a concentration that prevents protein synthesis, does not affect the appearance of enzyme in the incubation medium, but the fat-cell enzyme activity is decreased in its presence. 3. The magnitude of the increase in total clearing factor lipase activity is unaffected by the omission of heparin from the medium. However, less enzyme is extracted in tis absence and the fat-cell activity increases. Cycloheximide again only affects the rise in cell activity and does not alter the activity in the incubation medium. 4. When serum in the incubation medium is replaced by casein, the distribution of enzyme between the cells and the medium is changed, but the magnitudes of the increases in total enzyme activity are similar. 5. These characteristics of the clearing-factor lipase response of isolated fat-cells differ in several respects from those observed earlier with intact adipose tissue from 24h-starved rats (Robinson & Wing, 1971; Cryer et al., 1973). The differences could be due, in part, to changes in the relative amounts of two different molecular forms of the enzyme that occur during the isolation of the fat-cells.     

Distribution of microtubules in prolactin cells of lactating rats

The intracellular distribution of microtubules was studied using serial sections of prolactin cells in anterior pituitary glands from lactating rats. Numerous microtubules were present in these cells following fixation with glutaraldehyde and osmium tetroxide. The greatest number of microtubules were present in the Golgi complex, situated around the perimeter and in association with the cisternae, vesicles and developing secretory granules. Microtubules were found in channels between groups of parallel cisternae of rough surfaced endoplasmic reticulum and in close proximity to small vesicles. They were also located adjacent to mitochondria, the plasmalemma, the nuclear envelope, and among mature secretory granules. Due to their orientation within the cell, it is suggested that the microtubules may act to direct the movement of organelles from one region of the cell to another and to give internal support to the cell.     

Biosystematics of the monocotyledoneae—flavonoid patterns in leaves of the liliaceae

In a leaf survey of 168 species of the Liliaceae, most of the major flavonoid classes were found to be represented in the family. Flavonols occurred most frequently: quercetin and kaempferol were detected in 40% and 42% of the sample respectively, while the flavones luteolin and apigenin were present in only 24% and 20% of the sample. Methylated derivatives, i.e. isorhamnetin, diosmetin and tricin were rare. Procyanidins were present in 17 species, flavonoid sulphates in only one species and flavone C-glycosides in only three species. Anthraquinone pigments were identified in species of Aloe Asphodeline and Asphodelus. Three new flavonoid glycosides were characterised during the course of the survey: diosmetin 7-diglucoside in Colchicum byzanthinum and tricin 7-fructosylglucoside and tricin 7-rutinoside-4′-glucoside in Hyacinthus orientalis cv. ‘Quean of the Pinks’. On the basis of the flavonoid survey, the subfamilies of the Liliaceae may be grouped into those containing flavonols only, those with flavones only or those having both flavonols and flavones. Members of the related families: Amaryllidaceae (17 species), Agavaceae (1 species) and Xanthorrhoeaceae (1 species) contained only flavonols. The subfamilies Scilloideae, Asphodeloideae and Melanthioideae show the most chemical variation whilst the Wurmbaeoideae and Lilioideae are the most homogeneous groups. The tribe Scilleae is unusual in that both flavone- and flavonol-containing genera occur and a wide variety of flavonoid types are represented. A comparison of the leaf flavonoids of the Liliaceae with those found in families related to the grasses showed that all except two classes of flavonoid compound (5-methylated flavones and 5-deoxyflavonoids) found in the Juncaceae. Cyperaceae, Palmae and Gramineae are present in the Liliaceae thus supporting the view that all four families could have arisen from Liliaceae-like ancestors.     

Measurement of fibrinogen-fibrin-related antigen in serum as aid to diagnosis of deep vein thrombosis in outpatients.

A study of serum levels of fibrinogen-fibrin-related antigen (F.R.-antigen) in outpatients presenting with clinical features suggesting deep vein thrombosis was undertaken. A raised serum level of this antigen (greater than 12 mg/1) is strong evidence in favour of the diagnosis of deep vein thrombosis. It is virtually conclusive evidence if other known causes of a raised level of the antigen are absent. On the other hand, a normal serum level of F.R.-antigen does not exclude even extensive thrombosis, and other objective techniques are required to substantiate the diagnosis.     

Role of lymphography in carcinoma of the prostate.

The results of bilateral pedal lymphography in 83 patients with adenocarcinoma of the prostate gland are presented. The patients were divided into two groups: 45 new cases and 38 late or old cases presenting several years after the onset of the disease. Altogether 25 of the new patients and 29 of the late patients had lymphographic evidence of lymph node metastases. The lymphogram results in relation to local tumour size, histological grade, the presence of skeletal metastases, and acid phosphatase levels are discussed. Of the new patients with T1 and T2 tumors--that is, those still localized within the prostatic capsule--41% had positive lymphograms. The inaccuracy of acid phosphatase estimations in detecting early extraprostatic spread is shown and compared with the greater accuracy of lymphography. Lymphography should be used as an initial investigation in all cases where aggressive therapy is being considered, and the importance of regular follow-up radiographs is emphasized.