Suppression of 5α-androstane-3β, 17β-diol hydroxylase activity in rat pituitary by cobalt protoporphyrin: Implications for testosterone homeostasis

Cobalt protoporphyrin (CoPP) administered subcutaneously to adult male rats caused a marked reduction in the conversion of 5α-androstane-3β-17β-diol (3β-adiol) to its main triol derivative (6α-atriol) by homogenates of the pituitary but not of the prostate or brain (ventromedial hypothalamus and cortex). No effect in the brain was observed when this heme analogue was infused intracerebroventricularly. 3β-adiol hydroxylase, the enzyme responsible for the reaction and whose main function is thought to be the elimination of dihydrotestosterone and its metabolites from target tissues, was also inhibited by CoPP and SKF-525A added in vitro. The reaction was microsomal and dependent on NADPH. It is proposed that the lack of reciprocal elevation of luteinizing hormone in the face of the low testosterone levels observed following treatment with CoPP may be due, in part, to increased levels of androstanediols. These metabolites accumulate because of increased production from testosterone and decreased conversion to their triol derivatives in the pituitary.     

Management of traumatic intracranial haematoma.

Deciding which head-injured patients should be transferred to a neurosurgical unit can be difficult. Traditional criteria emphasise the development of deteriorating responsiveness but lead to delayed diagnosis and to avoidable mortality and morbidity. To discover if a more liberal admission policy improved results a study was conducted analysing data collected prospectively from 683 patients who had a traumatic intracranial haematoma evacuated in the Glasgow neurosurgical unit between 1974 and 1980. In the first four years, before the change in policy, mortality was 38% but decreased to 29% afterwards. This reflected a reduction in the proportion of patients who talked after injury but who deteriorated into coma before operation--that is, 31% before the change in policy, 16% afterwards. If the potential benefits of CT scanning in the management of head injuries are to be realised patients must be scanned sooner than in the past. This will usually mean that more patients should go to a neurosurgical unit and that simple criteria for transfer should be established.     

Analysis of the initial stages of plant protoplast development using 33258 Hoechst: reactivation of the cell cycle

A microfluorimetric procedure, employing the fluorescent stain 33258 Hoechst, has been developed for the investigation of the process of DNA synthesis during the initial stages of culture of tobacco ( N. tabacum cv. Xanthi) leaf protoplasts.
In this system, the freshly-isolated protoplasts exhibited a unimodal distribution of nuclear DNA content characteristic of the diploid state. The almost immediate onset of DNA synthesis during culture resulted in a doubling of nuclear DNA levels prior to the first mitoses. Although the majority of the protoplasts subsequently entered into synchronous mitosis and cell division, a proportion of the remainder developed into large polyploid cells. Upon further culture, the polyploid cells became subdivided into clusters of small diploid cells. Measurement of total cell protein and cell volumes during culture indicated that a relationship existed between these parameters and the initiation of mitosis. The significance of these observations is discussed.     

Distribution of podolactone-type plant growth inhibitors in the coniferae

Plant growth inhibitors of the podolactone-type have been detected by bioassay in ten further species of Podocarpus. The most active extracts in P. elatus were from root tips, root cortex and very young leaves. Fifty-seven other conifers were examined for this type of activity. It is present in Cephalotaxus harringtonia where it is probably due to the presence of harringtonolide, which, like momilactone B from rice husks, shows podolactone-type inhibition of the growth of etiolated dwarf pea hooks.     

In vitro metabolism of possible ecdysone precursors by the prothoracic glands of the tobacco hornworm, Manduca sexta

3 beta, 14 alpha-Dihydroxy-5 alpha-7-en-6-one (5 alpha-ketodiol) (1) is metabolized by the prothoracic glands to 2,22-dideoxy-5 alpha-ecdysone (4) and 2-deoxy-5 alpha-ecdysone (3) but not to ecdysone (5) or any other 5 beta-metabolites. Similarly, 3 beta,5 alpha,14 alpha-trihydroxy-cholest-7-en-6-one (5 alpha-ketotriol) (8) is hydroxylated at C-22 and C-25 (9,10) of the side chain. However, 3 beta,14 alhpa-dihydroxy-cholesta-4,7-diene-6-one (ketodienediol) (11) is not metabolized. The absence of 2 beta-hydroxymetabolites for substrates (1) and (8) implies that hydroxylation at C-2 can occur only when the A-B rings are cis fused (5 beta-configuration). By contrast, the enzyme complexes that introduce hydroxyls at C-22 and C-25 do not exhibit a preference for cis over trans fusion and appraently cannot recognize the planar A-B ring configuration.     

Trophoblast transferrin and transferrin receptors in the host--parasite relationship of human pregnancy.

Transferrin and specific transferrin receptors are demonstrated on the microvillous surface of syncytiotrophoblast in human immature and term placentae by immuno histological techniques with the use of light and electron microscopy. That the distribution of transferrin is limited to the materno-foetal interface supports the hypothesis that binding of maternal transferrin to trophoblast receptors is involved in the process of iron transport to the foetus. Parallel studies with baboon placentae demonstrate the presence of trophoblast receptors which bind both baboon and human transferrin, thereby putting forward an experimental model which might be used to test the biological significance of placental transferrin receptors in primates. In addition, investigation of a large number of human cell lines shows that many transformed cells, but no normal cells (such as blood lymphocytes) or cells from primary culture (such as neonatal foreskin fibroblasts), possess the ability to bind transferrin to their membranes. These findings suggest that transferrin receptors may play important biological roles in addition to that of iron transport from mother to foetus. One such role could be the limitation of iron in intervillous spaces, thus depriving iron-requiring microorganisms of iron, hence serving as a non-specific factor of resistance for placentae. Another role for foetal transferrin receptors on trophoblasts could be to bind maternal transferrin at the materno-foetal interface, thus frustrating maternal immunosurveillance. This is similar to a mechahism used by schistosomes in the host-parasite relation where host proteins are bound by the parasite to escape immunological recognition. The presence of transferrin receptors on transformed cells suggests that this mechanism might also be employed by tumour cells. Finally, in view of previous studies which show that transferrin is required by stimulated lymphocytes to pass from the G1 to the S phase of cellular replication, it is proposed that trophoblast transferrin receptors could limit the amount of transferrin in intervillous spaces and thus impede the proliferation and possible cytotoxicity of maternal activated lymphocytes at the materno-foetal interface.     

Tissue microenvironment and the genetic control of hair pigment patterns in mice

This study was conducted to assess microenvironmental variability within integumental tissue of genetically identical mice with respect to a specific cellular response: cyclic synthesis of yellow and black pigment by hair bulb melanocytes. Crosses were performed within and between inbred strains of mice that were isogenic with the exception of a single gene substitution at the agouti locus. Agouti locus genes included the A^vy, A^w, A, a^td, a^t, a^x, a^m, and a alleles. The pigment patterns of dorsal, flank, and ventral hairs of the first and third hair generations and of hairs growing in special integumentary areas such as the pinna, tail, and hind foot were studied. It was found that the amount of yellow pigment synthesized by hair bulb melanocytes within genetically identical mice is both agedependent and conditioned by the integumentary environment. Furthermore, the special integumentary regions produce hairs with a variety of pigment patterns in which the distribution and relative amounts of black and yellow pigments do not necessarily conform to dominance relationships expected among agouti locus alleles as judged by their effects on the pigmentation of the dorsal pelage. We conclude that within genetically uniform integumental tissues, microenvironmental differences occur and are reflected as alterations in the metabolic pattern of differentiated cells.     

Structure of root nodules formed by Rhizobium on the non-legume Trema cannabina var. scabra

The structure of the nodules formed by Rhizobium on the non-legume Trema cannabina var. scabra was studied using the light microscope. The overall features of the nodules showed greater resemblance to the non-legume rather than the legume nodule. Nodule squashes yielded bundles of infection threads and bacteroids with morphological differences from rhizobial cells grown on yeast-mannitol-glucose agar. Two types of cell infection occurred within the bacterial zone; plant cells were either, like legumes, filled with rhizobia released from the infection threads (less than one third of infected cells) or were filled with the extensive growth and development of the infection thread. The rate of nitrogen fixation in the Trema nodule was high. It seemed that host cells filled with threads were active in N fixation.     

Unexpected beta adrenergic effects of the antitumor agent, cyclocytidine, on rat salivary glands.

In addition to its potent antileukemic properties, cyclocytidine has a sialogogue action that depends on stimulation of beta adrenergic ereceptors of salivary glands. Furthermore, when chronically administered (for 3 days), cyclocytidine caused enlargement of parotid and submaxillary glands and heart that resembled the hypertrophy caused by chronic isoproterenol administration. The salivas evoked by cyclocytidine also closely resembled those evoked by isoproterenol, and were extremely viscous, and high in K+, (121 plus or minus 5.6, for submaxillary, and 42 plus or minus 2.9, for parotid), low in flow rate (0.007 mg/min times mg) and parotid saliva contained high concentrations of amylase (805 plus or minus 33 mg/mg gland). Cyclocytidine also caused marked emptying of parotid gland amylase. The cyclocytidine-induced salivary flow and gland emptying of amylase were prevented for 90 min when propranolol (but not dibenzyline or atropine) was administered prior to injection of the cyclocytidine. In addition, when the superior cervical ganglion was acutely removed, administration of cyclocytidine elicited salivary flow from the denervated as well as the innervated glands. These findings suggest that cyclocytidine does not affect salivary glands through indirect central or ganglionic actions. Cyclocytidine action does not exclusively involve beta receptors, since even in the presence of propranolol, secretory flow was evident after 90 min but when dibenzyline was given with the propranolol, complete blockade of cyclocytidine-stimulated saliva was effected. The dominant effect is, however, a beta adrenergic one. The undesirable side effects of cyclocytidine (parotid pain, postural hypotension, and cardiac hypertrophy) probably stem chiefly from its beta adrenergic properties and might be eliminated (or at least modified) by administration of propranolol with the cyclocytidine.