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Biomedical subjects

G Shaw

Publications and source records attributed to G Shaw.

At least 19 recordsLinked to original sources
PubMed1992

Introduction of intersubunit disulfide bonds in the membrane-distal region of the influenza hemagglutinin abolishes membrane fusion activity.

Influenza virus hemagglutinin (HA) mediates viral entry into cells by a low pH-induced membrane fusion event in endosomes. A number of structural changes occur throughout the length of HA at the pH of fusion. To probe their significance and their necessity for fusion activity, we have prepared a site-directed mutant HA containing novel intersubunit disulfide bonds designed to cross-link covalently the membrane-distal domains of the trimer. These mutations inhibited the low pH-induced conformational changes and prevented HA-mediated membrane fusion; conditions that reduced the novel disulfide bonds restored membrane fusion activity. We conclude that structural rearrangements in the membrane distal region of the HA are required for membrane fusion activity.

Animals↗
PubMed1992

Human T-lymphotropic virus type I-associated myelopathy in patients with the acquired immunodeficiency syndrome.

We describe two cases of serologically confirmed human T-lymphotropic virus type I (HTLV-I)-associated myelopathy involving North American men coinfected by the human immunodeficiency virus type 1. Our first patient suffered from a gradually progressive spastic paraparesis for 10 years prior to presenting with Kaposi's sarcoma, while our second patient developed subacutely progressive spastic paraparesis in the setting of full-blown acquired immunodeficiency syndrome. Autopsy examination of the spinal cords from these two cases revealed widespread axonal loss and demyelination principally involving the lateral columns of case no. 1 and the lateral and anterior columns of case no. 2. Vascular sclerosis and hyalinization were prominent in both cases, but in neither was there a conspicuous inflammatory component. In case no. 2, HTLV-I mRNA was not detected by in situ hybridization, but HTLV-I proviral DNA sequences were detected in this case by polymerase chain reaction. Neither case exhibited multinucleated cell (human immunodeficiency virus type 1) myelitis, vacuolar myelopathy, or evidence of HTLV-II infection by polymerase chain reaction assay.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Steroid hormone content of the gonads of the tammar wallaby during sexual differentiation.

The gonads of the tammar wallaby, Macropus eugenii, are sexually indifferent at birth (Day 0) despite the fact that phenotypic sexual differentiation has already commenced as evidenced by the presence of a scrotum in males and mammary anlagen in females. The seminiferous cords of the testis first become clearly recognizable on Day 2 of pouch life, and ovarian differentiation is recognizable by Day 10. To monitor the endocrine development of the gonads during sexual differentiation of the urogenital tract, we measured the steroid hormone content in 92 pools of gonads from male and female tammar pouch young from the day of birth to 206 days of pouch life. Progesterone, estradiol, and dihydrotestosterone concentrations were low (less than 0.05 ng/mg protein) in both ovaries and testes at all stages examined, and testosterone concentrations were uniformly low in ovaries. Testosterone concentrations in testes were low on Days 0-4, averaging about 0.2 ng/mg protein; they rose by Days 5-10 to an average of 0.9 ng/mg protein, remained elevated until about Day 40, and thereafter fell to values similar to those in the ovaries. The phallus and urogenital sinus were able to convert testosterone to dihydrotestosterone from the earliest stages examined (Days 10 and 11). Thus in the tammar wallaby, as in eutherian mammals, testosterone is the androgen secreted by the developing testis, and dihydrotestosterone is formed in certain androgen target tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1992

Identification of spinal cord polypeptides related to glial fibrillary acidic protein (GFAP).

Spinal cord cytoskeletal preparations from three different mammalian species contain several polypeptides in the SDS-PAGE molecular weight range 100-220 kDa which are recognized by all members of a panel of antibodies to glial fibrillary acidic protein (GFAP) and by anti-IFA, a panspecific intermediate filament protein antibody. The polypeptides are not recognized by antibodies to other intermediate filament proteins or to ubiquitin. The proteins coelute with GFAP in ion-exchange chromatography, cosediment with GFAP under filament assembly conditions, produce similar chemical digest patterns and have an amino acid profile close to that of pure GFAP, all properties expected for covalent GFAP multimers. Further experiments provide evidence for the existence of such multimeric complexes in vivo.

Amino Acids↗
PubMed1991

Role of AUUU sequences in stabilization of granulocyte-macrophage colony-stimulating factor RNA in stimulated cells.

RNAs for transiently expressed genes such as oncogenes and cytokines, including granulocyte-monocyte colony-stimulating factor (GM-CSF), have a short half-life (T1/2). A cluster of AUUU sequences identified in the 3' untranslated (UT) region of these RNAs has been implicated in controlling stability of these transcripts. We examined the role of AUUU sequences in mRNA stability of GM-CSF after stimulation of cells. Human fibroblasts (W138) were stably transfected with chimeric constructs containing the beta-globin gene linked to a 52-bp tail of GM-CSF containing either eight ATTTT (pNEOR beta G-AT) or eight repeats in which the AT sequences have been changed to GC sequences (pNEOR beta G-GC). Data confirmed that AUUU sequences in 3'UT region of GM-CSF play a major role in GM-CSF RNA instability. Stimulators of protein kinase C (PKC), cycloheximide (CHX), sodium fluoride (NaF), and, to a more limited extent, interleukin-1 beta (IL-1 beta), appear to stabilize GM-CSF RNA through these AUUU sequences, but tumor necrosis factor-alpha (TNF-alpha) induces stabilization of GM-CSF RNA through a mechanism independent of their AUUU sequences.

Base Sequence↗
PubMed1991

Synthesis of 4- and 5-amino-1-(2-deoxy-D-erythro-pentofuranosyl)imidazole nucleosides by chemical and biotransformation methods.

(2-Deoxy-D-erythro-pentofuranosyl)imidazole nucleosides have been synthesised by glycosylation of the sodium salt of ethyl 5-aminoimidazole-4-carboxylate with 2-deoxy-3,5-di-O-p-toluoyl-alpha-D-erythro-pentofuranosyl chloride. Glycosylation of ethyl 5-aminoimidazole-4-carboxylate with 2-deoxy-beta-D-erythro-pentofuranose was also achieved enzymically using E. coli, immobilised by ionotropic gelation in an alginate gel, with 2'-deoxyuridine as glycosyl donor. 5-Amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)imidazole-4-carboxylic acid 5'-phosphate and 4-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)imidazole-5-carboxylic acid 5'-phosphate were synthesised by phosphorylation of the respective nucleosides and examined as inhibitors of phosphoribosylaminoimidazole carboxylase (EC 4.1.1.21) and phosphoribosylaminoimidazolesuccinocarboxamide synthetase (EC 6.3.2.6), which are involved in the de novo biosynthesis of purine nucleotides.

Biotransformation↗
PubMed1991

Contraceptive effects of extended lactational amenorrhoea: beyond the Bellagio Consensus.

We have recorded the duration of lactational anovulation and amenorrhoea in a well-nourished group of Australian women who breastfed their babies throughout the study. The data enabled us to compare the theoretical cumulative probability of conception among breastfeeding women who had unprotected intercourse irrespective of their menstrual status with that of those who had unprotected intercourse only during lactational amenorrhoea. Breastfeeding alone is not an effective form of contraception, since all the women in our study resumed normal ovulation while still breastfeeding. However, among women who have unprotected intercourse only during lactational amenorrhoea but adopt other contraceptive measures when they resume menstruation, only 1.7% would have become pregnant during the first 6 months of amenorrhoea, only 7% after 12 months, and only 13% after 24 months. Thus for our women it would be possible to extend the Bellagio Consensus Conference guidelines which stated that lactational amenorrhoea can only be relied on as a contraceptive for the first 6 months post-partum in women who are fully or almost fully breastfeeding. The lactational amenorrhoea method can be relied on for excellent contraceptive protection in the first 6 months of breastfeeding, irrespective of when supplements are introduced into the baby's diet; for women who continue to breastfeed the method can also give good protection for up to 12 months post partum. Once menstruation has returned, other forms of contraception are essential to prevent pregnancy.

Amenorrhea↗
PubMed1991

A molecular dissection of the carboxyterminal tails of the major neurofilament subunits NF-M and NF-H.

We have initiated a multidisciplinary project that aims to dissect and ultimately define the functions of the long and unusual C-terminal "tail" sequences of the two high molecular weight neurofilament subunits, NF-M and NF-H. A series of recombinant fusion proteins containing selected NF-M and NF-H tail sequences were constructed using appropriate cDNAs. These fusion proteins were used to further define the epitopes for a variety of widely used neurofilament antibodies, including NN18 and N52, which are now available commercially from several companies. We also measured the SDS-PAGE mobility of the fusion proteins and found that, like the native neurofilament tails, the fusion proteins ran considerably slower than predicted from their molecular weight. Since all fusion proteins produced so far exhibit this characteristic we conclude that all segments of the NF-M and NF-H tail share this unusual property. Finally we were able to produce novel and potentially useful polyclonal and monoclonal antibodies to selected segments of NF-M and NF-H sequence. These antibody studies showed that the extreme C-termini of NF-M and NF-H are immunologically absolutely distinct from one another and also indicate that the extreme C-terminus of NF-M is immunologically much more conserved than the analogous region of NF-H. These findings are in complete agreement with our conclusions derived from amino acid sequence analysis, and further underline the possible functional importance of the extreme C-terminus of NF-M. We also show that the unusual immunological properties of the bovine NF-M tail we have previously observed do not extend to the extreme C-terminal region, which appears immunologically no different from the analogous region of other NF-M molecules. The peculiarities of bovine NF-M could be explained by the presence of a KSP motif that resembles the NF-H KSP prototype.

Animals↗
PubMed1991

Symptomatic intraventricular xanthogranulomata. A report of 2 cases.

Intraventricular xanthogranulomata may occasionally be seen as incidental findings at post-mortem. It is however, exceptionally rare for them to become symptomatic, but if they do, it is usually attributable to obstruction of the CSF pathways. Two further symptomatic cases are presented and the literature is reviewed. Treatment is surgical excision, but stereotactic biopsy should be avoided due to the often impenetrable nature of the capsule.

Adult↗
PubMed1991

Diuretic and saliuretic effects of 1,3-dipropyl-8-cyclopentylxanthine, a selective A1-adenosine receptor antagonist.

We have previously shown that 8-phenyltheophylline (8-PT), a non-selective antagonist at adenosine A1- and A2-receptors, has a diuretic effect. In this study, the diuretic and adenosine antagonist effects of the A1-receptor selective compound 1,3-dipropyl-8-cyclopentylxanthine (CPX) have been examined in the conscious rat. CPX (0.1 and 0.3 mg kg-1 i.v.) significantly attenuated bradycardic but not hypotensive responses evoked by adenosine. In contrast, 8-PT (3 mg kg-1 i.v.) significantly antagonized both adenosine-induced bradycardia and hypotension. CPX (0.1 and 0.3 mg kg-1 i.v.) evoked a dose-related diuretic and saliuretic response in the conscious rat. These results indicate that the diuretic effects of adenosine antagonists are associated with blockade of the A1-receptor sub-type.

Adenosine↗
PubMed1991

Stress management for irritable bowel syndrome: a controlled trial.

Thirty-five patients with irritable bowel syndrome were randomized to receive treatment in a stress management programme or conventional therapy which included the antispasmodic Colpermin. The stress management programme involved a median of six 40-min sessions with a physiotherapist during which patients were helped to understand the nature of their symptoms, their relationship to stress and were taught relaxation exercises. Two thirds of those in the stress management programme found the programme effective in relieving symptoms and experienced fewer attacks of less severity. This benefit was maintained for at least 12 months. Few of those given conventional management had any benefit. A stress management programme would appear to be of value for patients with irritable bowel syndrome.

Adult↗
PubMed1991

Study of ascitic fluid in relation to systemic and portal venous blood in hepatic cirrhosis.

Twenty uncomplicated cases of cirrhosis of liver, proved by liver biopsy, and free from other systemic diseases were studied. Glucose (pre- and postprandial) and electrolytes (Na+, K+, Cl-) values were compared to those of systemic and portal venous blood. Chloride level in ascitic fluid was found to be significantly high in cirrhosis, as compared to portal and systemic venous blood. Sodium and glucose levels were similar in ascitic fluid and portal venous blood except in two cases complicated with tuberculous peritonitis, where pre- and postprandial glucose levels were considerably low. In 55% cases, there was impaired glucose tolerance, as measured by pre- and postprandial glucose levels in systemic venous blood.

Adolescent↗
PubMed1991

Kinetics of the DNA binding of 2-substituted anthraquinones.

The DNA-binding properties of the 2-substituted-1,4-dihydroxyanthraquinones 5-12 were examined. Compounds 5 and 6 were synthesized in this study, 7-12 were already available. Spectral studies were consistent with intercalation of 5, 6 and 8 into DNA. Affinity constants were in the range of 3 x 10(4)M-1. Compounds 7 and 10-12 showed no DNA binding, presumably being sterically excluded from binding. The kinetics of the DNA interaction of 5, 6 and 8 were studied. There is a biphasic process. This may reflect an initial reaction, with drug from this first mode of binding moving into the second binding mode (a sequential process) or independent binding of drug in two sets of sites (a parallel process). The methods used in this study do not allow us to discriminate between these models. However, if the parallel binding model is correct, the compounds show sequence selectivity of binding, and provide a lead for further development of neutral DNA-binding ligands with sequence selectivity.

Anthraquinones↗