Mortality rates in diabetic patients from a community-based population.
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Adolescent↗
Biomedical subjects
M Pierce
Publications and source records attributed to M Pierce.
Teenage mothers as breastfeeders: attitudes and behaviour.
Surveys have repeatedly shown that teenage mothers are less likely to breastfeed than older mothers. A sample of 55 young mothers and expectant mothers contacted through agencies caring for young mothers revealed that decisions about breastfeeding are sometimes left till late in the pregnancy, and that breastfeeding is often of short duration. Only about half had discussed breastfeeding with a health worker. As with older mothers, the partners and the teenagers' own mothers often influenced their decision, sometimes in a hostile way. Many young mothers had never witnessed breastfeeding at first-hand. These results suggest ways in which breastfeeding could be more successfully promoted among young mothers.
Adolescent↗
Jewish and Celtic attitudes to breast feeding compared.
OBJECTIVE: To examine reasons for the high rate of breast feeding among one UK ethnic group (Jews) and the low rate among Celtic (Scots and Irish) populations. DESIGN: A manual literature search of ethnic variation in breast feeding rates in the UK was conducted over several years. A computerised search yielded 31 additional references. Seven of these were added. ANALYSIS: Positive Jewish attitudes to breast feeding were underpinned by scriptural references, and rates of breast feeding were found to be especially high among Orthodox samples in the UK and Israel. Low Scottish and Irish rates appear to reflect prudishness, fashion, and possibly poor health. Reasons for falling rates among these populations in the twentieth century were not clear. IMPLICATIONS FOR PRACTICE: Health education needs to address cultural attitudes throughout society if effective change is to be introduced, and the overall rate of breast feeding is to be increased.
Attitude to Health↗
Regulation of N-acetylglucosaminyltransferase V and Asn-linked oligosaccharide beta(1,6) branching by a growth factor signaling pathway and effects on cell adhesion and metastatic potential.
Recent evidence demonstrates that the changes in the size of N-linked oligosaccharides that correlate with cell transformation and tumorigenicity are due at least in part to the regulation of expression of a glycosyltransferase involved in the branching of N-linked structures, N-acetylglucosaminyltransferase V or GlcNAc-T V. Studies have shown that the increases in GlcNAc-T V expression after oncogenic transformation are most likely caused by direct effects on the GlcNAc-T V promoter by the Ets family of transcriptional activators, which are up-regulated by a cellular proliferation signaling pathway. This pathway begins with growth factor receptors that activate tyrosine kinases at the cell surface and proceeds through src, ras, and raf. Additional evidence for the association between cellular proliferation and GlcNAc-T V expression will be presented, as well as a discussion of the effects of beta(1,6) branching on several of the phenotypes of oncogenically transformed cells, including metastatic potential.
Animals↗
Cloning and expression of a Xenopus laevis oocyte lectin and characterization of its mRNA levels during early development.
cDNA clones encoding a soluble, calcium-dependent, melibiose-binding lectin from Xenopus laevis oocytes have been isolated, characterized, and expressed in bacteria. This lectin has been shown by others to be localized in oocyte cortical granules where it ultimately is released and participates in the formation of the fertilization envelope. A lectin with similar specificity has been purified by others from blastula and immunolocalized to specific locations in developing embryos, which suggests it may also function after fertilization in regulating cell adhesion and migration. We have used melibiose affinity chromatography to isolate the oocyte lectin (monomer molecular masses of about 45 and 43 kDa) and shown that after exhaustive treatment with N-glycanase, only one major protein band at 35 kDa was observed, suggesting that a single polypeptide with variable N-linked glycosylation is expressed in the oocyte. After obtaining internal peptide sequences, a PCR-based cloning approach allowed the isolation of full length cDNAs from an ovary lambda gt11 library encoding a protein of 313 amino acids with three potential N-linked oligosaccharide sites. Although this lectin, termed XL35, requires calcium ions for oligosaccharide binding, its sequence does not contain the sequence motif defined for "C-type" lectins. A 6-Histagged from of the lectin was expressed in E. coli and purified on a Ni(2+)-NTA column from bacterial extracts. The recombinant lectin was active using an agglutination assay, and this activity was inhibitable by EDTA and melibiose, properties exhibited by the native lectin. Southern blot analysis revealed a single hybridizing band, arguing against the existence of a multigene family. Northern blot analysis demonstrated that the lectin mRNA is expressed in oocytes and remains at relatively high levels through late gastrulae, continuing until tadpole stages. The persistence of the lectin mRNA, coupled with results from earlier studies, strongly suggests that XL35 is zygotically expressed and functions during morphogenesis.
Amino Acid Sequence↗
Clarithromycin and ethambutol with or without clofazimine for the treatment of bacteremic Mycobacterium avium complex disease in patients with HIV infection.
OBJECTIVE: To compare the efficacy of two- and three-drug regimens for treating Mycobacterium avium complex (MAC) bacteremia in patients with AIDS. DESIGN: Randomized open-label clinical trial. SETTING: Outpatient HIV specialty centers' clinics. PATIENTS: A total of 106 adults with AIDS and MAC bacteremia. INTERVENTIONS: Patients were treated with clarithromycin 500 mg twice daily and ethambutol 800-1,000 mg daily and were randomized to receive clofazimine 100 mg daily or no clofazimine. MAIN OUTCOME MEASURES: Quantitative blood MAC cultures, symptoms, adverse reactions and survival. RESULTS: Patients randomly assigned to three drugs had significantly higher baseline colony counts of MAC in blood than patients receiving two drugs. The proportion of patients becoming culture-negative was 65% in the two-drug group and 54% in the three-drug group. The median time to negative culture was 58 days for patients in the two-drug and 63 days for the three-drug group. At the last visit during treatment, the mean reduction in colony forming units/ml of MAC in blood was 1.8 log10 for the two-drug group and 2.3 log10 for the three-drug group. Improvement in fever and night sweats was reported by 87 and 89% of the two-drug patients and 84 and 86% of the three-drug patients. During the study, 38% of two-drug patients and 61% of three-drug patients died (P = 0.032), and time to death was shorter in patients treated with three drugs (P = 0.012). In a multivariate analysis, both assignment to clofazimine and high baseline colony counts of MAC bacteremia were significantly associated with death (P < 0.05). CONCLUSION: The addition of clofazimine to a regimen of clarithromycin and ethambutol for MAC bacteremia in AIDS patients does not contribute to clinical response and is associated with higher mortality.
AIDS-Related Opportunistic Infections↗
Gabapentin monotherapy: I. An 8-day, double-blind, dose-controlled, multicenter study in hospitalized patients with refractory complex partial or secondarily generalized seizures. The US Gabapentin Study Group 88/89.
We evaluated the efficacy and safety of gabapentin administered as monotherapy in an 8-day, randomized, double-blind, dose-controlled, parallel-group, multicenter study comparing dosages of 300 and 3,600 mg/d gabapentin in 82 hospitalized patients whose antiepileptic medications had been discontinued for seizure monitoring. Seizures under study were complex partial seizures with or without secondary generalization. Patients exited the study if they experienced a protocol-defined exit event indicating lack of efficacy. Time to exit was significantly longer (p = 0.0001) and completion rate was significantly higher (53% versus 17%; p = 0.002) for patients receiving 3,600 mg/d gabapentin. Gabapentin was well tolerated by patients in both dosage groups, and no patients exited the study due to adverse events, despite rapid initiation of full dose within 24 hours. These results demonstrate that gabapentin has anticonvulsant activity and is well tolerated when administered as monotherapy in patients with refractory partial seizures.
Acetates↗
Gabapentin monotherapy: II. A 26-week, double-blind, dose-controlled, multicenter study of conversion from polytherapy in outpatients with refractory complex partial or secondarily generalized seizures. The US Gabapentin Study Group 82/83.
This study evaluated gabapentin monotherapy in 275 patients with medically refractory complex partial or secondarily generalized seizures who were taking one or two antiepileptic drugs (AEDs). Following an 8-week baseline, patients received randomized dosages of gabapentin (600, 1,200, or 2,400 mg/d) during a 26-week double-blind phase comprising 2 weeks gabapentin add-on therapy, an 8-week AED taper, and a 16-week gabapentin monotherapy period. Patients exited the study if they experienced a protocol-defined exit event. Results of outcome measures, including time to exit, completion rate, and mean time on monotherapy, showed no significant differences among dosage groups. Possible reasons for this lack of a dose-response relationship include withdrawal seizures and the limited range of gabapentin dosages studied. Overall, 20% of patients completed the study. Completion rates were higher among patients who had discontinued one AED (23%) than two AEDs (14%), and higher among patients who were not withdrawn from carbamazepine (27%) than among those who were (16%).
Acetates↗
Emerging infectious diseases: new and resistant strains of HIV.
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Anti-HIV Agents↗
A randomized trial of clarithromycin as prophylaxis against disseminated Mycobacterium avium complex infection in patients with advanced acquired immunodeficiency syndrome.
BACKGROUND: Disseminated infection with Mycobacterium avium complex is the most common opportunistic infection in patients with advanced stages of the acquired immunodeficiency syndrome (AIDS). We studied the efficacy and safety of prophylactic treatment with clarithromycin, a macrolide antibiotic. METHODS: We conducted a randomized, placebo-controlled, double-blind study of clarithromycin in patients with AIDS in the United States and Europe. Entry criteria included blood cultures that were negative for M. avium complex, a Karnofsky performance score of 50 or higher, a CD4 cell count of 100 or less per cubic millimeter, and a life expectancy of at least six months. RESULTS: After the first interim analysis, the study was stopped. M. avium complex infection developed in 19 of the 333 patients (6 percent) assigned to clarithromycin and in 53 of the 334 (16 percent) assigned to placebo (adjusted hazard ratio, 0.31; 95 percent confidence interval, 0.18 to 0.53; P<0.001). During the follow-up period of about 10 months, 32 percent of the patients in the clarithromycin group died and 41 percent of those in the placebo group died (hazard ratio, 0.75; P=0.026). In the clarithromycin group, isolates from 11 of the 19 patients with M. avium complex infection were resistant to clarithromycin. Prophylaxis with clarithromycin was associated with an increased incidence of taste perversion (11 percent in the clarithromycin group vs. 2 percent in the placebo group, P<0.001) and rectal disorders (8 percent vs. 3 percent, P = 0.007); however, the frequency of more severe adverse events was similar in the two groups (7 percent and 6 percent, respectively). CONCLUSIONS: In patients with advanced AIDS, the prophylactic administration of clarithromycin is well tolerated, prevents M. avium complex infection, and reduces mortality.
AIDS-Related Opportunistic Infections↗
Swallowing disorders in head and neck cancer patients treated with radiotherapy and adjuvant chemotherapy.
The nature of swallowing problems was examined in nine patients treated primarily with external-beam radiation and adjuvant chemotherapy for newly diagnosed tumors of the head and neck. All subjects underwent videofluorographic examination of their swallowing. Three analyses were completed, including the following: observations of motility disorders, residue, and aspiration; temporal analyses; and biomechanical analyses. Oropharyngeal swallow efficiency was calculated for the first swallow of each bolus. Swallow motility disorders were observed in both the oral and pharyngeal stages. Seven of the nine patients demonstrated reduced posterior tongue base movement toward the posterior pharyngeal wall and reduced laryngeal elevation during the swallow. Oropharyngeal swallow efficiency measures were significantly lower in the nine irradiated patients than in age-matched normal subjects. Between patients and normal subjects, significant differences were found in the measures of timing and distance of pharyngeal structural movements during the swallow, as well as in the measures of coordination during the swallow. Although treatment of head and neck cancer with external-beam radiation is designed to provide cancer cure and preserve organ functioning, oral and pharyngeal motility for swallow can become compromised if external-beam radiation treatment is provided to either the larynx or tongue base regions.
Adult↗
IS6110-based PCR methods for detection of Mycobacterium tuberculosis.
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DNA Transposable Elements↗
Blood pressure measurement in the community: do guidelines help?
The measurement of blood pressure (BP) is a crucial part of clinical assessment and hypertension management, and is commonly performed inaccurately despite the publication of National and International consensus guidelines for its measurement. There have been no previous reports on the self-reported knowledge-base of General Practitioners (GPs) and Practice Nurses (PNs) with regard to BP measurement. A postal questionnaire survey was conducted of 831 community-based practitioners (550 GPs and 281 PNs) in north west London. The overall response rate was 61%. Previous education in BP measurement was recorded in 87% of the GPs and 95% of the nurses. Precision factors were recorded for the GPs and nurses respectively including rounding up or down (GP 67%, PNs 48%), routine use of diastolic phase V (GP 63%, PNs 70%), reading the BP to the nearest 2 mm mercury (GP 54%, PNs 70%) and failure to use a large BP cuff in the past 4 weeks (GP 33%, PNs 26%). Only 12% of the GPs and 19% of the nurses were able to name the source of the published guidelines. Overall the nurses had a statistically significantly greater knowledge base than the GPs, and both community groups had a greater knowledge for core questions than hospital practitioners from two previous surveys. Knowledge of a guideline source was associated with improved self-reported BP technique. There was a difference between reading and recording accuracy which deserves further study. These results show that there are important gaps in the knowledge of community practitioners with regard to the technique of BP measurement.
Blood Pressure Determination↗
Remodeling of mouse milk glycoconjugates by transgenic expression of a human glycosyltransferase.
The mammary gland is a unique biosynthetic tissue that produces a variety of species-specific glycoconjugates, but the factors regulating the production of specific glycoconjugates are not well understood. To explore the underlying regulation, a fusion gene containing a cDNA encoding the human alpha 1,2-fucosyltransferase (alpha 1,2FT), which generates the H-blood group antigen, flanked by the murine whey acidic protein promoter and a polyadenylation signal, was introduced into mice. Milk samples from transgenic animals contained soluble forms of the alpha 1,2FT, as revealed by Western blots of milk samples using an anti-alpha 1,2FT antiserum and by the demonstration of alpha 1,2FT enzyme activity. Milk from transgenic animals also contained large quantities of 2'-fucosyllactose (Fuc alpha 1-2Gal beta 1-4Glc) and modified glycoproteins containing the H-antigen, whereas milk from control animals lacked these glycoconjugates. Expression levels of 2'-fucosyllactose were high in most animals and represented 1/3 to nearly 1/2 of the total milk oligosaccharides. These results demonstrate that heterologous transgenic expression of a glycosyltransferase can result in the expression of both the transgene and its secondary gene products and that the structures of milk oligosaccharides can be remodeled depending on expression of the appropriate enzyme. Furthermore, these results suggest that the lactating mammary gland may be a unique biosynthetic reactor for the production of biologically active oligosaccharides and glycoconjugates.
ABO Blood-Group System↗
Effects of 12-O-tetradecanoylphorbol-13-acetate on estrogen receptor activity in MCF-7 cells.
The effects of long term treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) on estrogen receptor (ER) expression in the human breast cancer cell line, MCF-7, were studied. This study demonstrates that treatment of cells with the phorbol ester blocked estrogen receptor activity. Treatment of cells with 100 nM TPA resulted in an 80% decrease in the level of ER protein and a parallel decrease in ER mRNA and binding capacity. Following removal of TPA from the medium, the level of ER protein and mRNA returned to control values; however, the receptor failed to bind estradiol. These cells also failed to induce progesterone receptor in response to estradiol. In addition, TPA treatment blocked transcription from an estrogen response element in transient transfection assays and inhibited ER binding to its response element in a DNA mobility shift assay. The estrogen receptor in treated cells was recognized by two monoclonal anti-ER antibodies and was not quantitatively different from ER in control cells. RNase protection analysis failed to detect any qualitative changes in the ER mRNA transcript. Mixing experiments suggest that TPA induces/activates a factor which interacts with the ER to block binding of estradiol. The effects of TPA on ER levels and binding capacity were concentration-dependent. Low concentrations of TPA inhibited estradiol binding without a decrease in the level of protein, whereas higher concentrations were required to decrease the level of ER protein. The effects of TPA appear to be mediated by activation of protein kinase C since the protein kinase C inhibitors, H-7 and bryostatin, block the effects of TPA on estradiol induction of progesterone receptor. TPA treatment had no effect on the level or binding capacity of the glucocorticoid receptor, indicating that the effects are not universal for steroid receptors. These data demonstrate that activation of the protein kinase C signal transduction pathway modulates the estrogen receptor pathway. The long term effect of protein kinase C activation is to inhibit estrogen receptor function through induction/activation of a factor which interacts with the receptor.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Purification and characterization of human serum N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase.
Many lysosomal enzymes are recognized and selected by a unique marker in the form of mannose 6-phosphate groups which are present exclusively on their N-linked oligosaccharides. Two enzymes act sequentially to catalyze the addition of mannose 6-phosphate groups to the proteins: N-acetylglucosamine phosphotransferase (GlcNAc phosphotransferase) and N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase (phosphodiester alpha-GlcNAcase). We report here the purification and partial characterization of phosphodiester alpha-GlcNAcase from human serum. The enzyme was purified over 600,000-fold by utilizing ammonium sulfate precipitation, fractionation on wheat germ agglutinin-Sepharose, Fe(3+)-chelating Sepharose, and Cu(2+)-chelating Sepharose, and renaturation from gel slices after sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The protein observed after renaturation and subsequent SDS-PAGE and silver staining had an apparent molecular mass of 118 kDa, which is slightly smaller than bovine liver phosphodiester alpha-GlcNAcase (Mullis et al. (1994) J. Biol. Chem. 269, 1718-1726). Serum enzyme activity does not require Triton X-100 and is not stimulated by its addition. These results suggest that the enzyme found in serum represents a form secreted after proteolysis in the Golgi of the membrane-bound enzyme. The serum enzyme hydrolyzed UDP-GlcNAc to UDP and GlcNAc and hydrolyzed GlcNAc-P-Man alpha Me into alpha MeMan-P and GlcNAc. The enzyme had no hydrolyzing activity toward UDP-GalNAc, UDP-Glc, [6-3H]GlcNAc beta 1-3Gal beta 1-4Glc, p-nitrophenyl-alpha-N- acetylglucosaminide, p-nitrophenyl-beta-N-acetylglucosaminide, p-nitrophenyl-alpha-N-galactopyranoside, or p-nitrophenyl-beta-N- galactopyranoside. The enzyme activity was strongly inhibited by UDP-GlcNAc and GlcNAc-1-phosphate, had a pH optimum between pH 6.0 and 7.0, and was inhibited by FeCl3, FeSO4, and CuSO4. The Km values for UDP-GlcNAc and GlcNAc-P-Man alpha Me were 0.94 and 0.45 mM, respectively. Over 77% of enzyme activity remained after incubation for 10 min at 70 degrees C, demonstrating an unusual thermostability of the serum enzyme.
Chromatography, High Pressure Liquid↗
Glycosyltransferase assay system utilizing an acylated glycopeptide acceptor.
A glycosyltransferase assay system was devised utilizing as acceptor a purified glycopeptide which was acylated at its N-terminus using caprylic (C8) anhydride. The glycopeptide contained five amino acids and an N-linked biantennary oligosaccharide, and it was purified from a pronase digest of bovine fibrinogen. Desialylation and beta-galactosidase digestion conditions were developed to produce asialo- and asialo-agalacto glycopeptides. Using fatty acid anhydrides, N-acylation conditions for these glycopeptides were then optimized. The products formed when the appropriate acylated glycopeptide was incubated with either of two N-acetylglucosaminyltransferases and UDP-[3H]N-acetylglucosamine were easily separated from unused sugar nucleotide and breakdown products by exploiting the affinity of the radiolabeled acylated glycopeptide products for pellicular C18 cartridges. The products of the enzymatic reactions bound quantitatively to the cartridges and could be eluted in small amounts of methanol. The Km values for the unacylated and acylated glycopeptide acceptors were similar when measured using either N-acetylglucosaminyltransferase V or the N-acetylglycosaminyltransferase which transfers N-acetylglucosamine in beta(1,3) linkage to N-acetyllactosamine (or lactose). This assay system can be used to measure many glycosyltransferases and other enzymes which transfer to N-linked biantennary oligosaccharides and is applicable to additional glycosyltransferases that transfer to other oligosaccharides which can be prepared as glycopeptides.
Acylation↗
Preparation of antisera to recombinant, soluble N-acetylglucosaminyltransferase V and its visualization in situ.
N-Acetylglucosaminyltransferase V (GlcNAc-T V) is a glycosyltransferase which transfers N-acetylglucosamine in beta(1,6) linkage to the alpha(1,6)-linked mannose residue of Asn-linked oligosaccharides. This enzyme is characterized by several unusual properties: GlcNAc-T V is the largest lumenal Golgi glycosyltransferase described thus far, and its multiple mRNA transcripts range from 4.5 to about 9.5 kb; GlcNAc-T V mRNA and activity are regulated by the src tyrosine kinase signalling pathway; in brain tissue, large levels of GlcNAc-T V mRNA are present, but only relatively low levels of catalytic activity can be detected; a lectin-resistant cell line, Lec4A, expresses active GlcNAc-T V which is mislocalized intracellularly. In addition, the cell surface oligosaccharide products of this enzyme have been hypothesized to regulate intercellular adhesion. In order to devise specific inhibitors of this enzyme it is necessary to understand its physical structure and how structural changes can influence its activity and localization. We have expressed milligram amounts of a soluble form of recombinant rat GlcNAc-T V, purified it from CHO cell-conditioned media, and used it to prepare specific antisera. This antisera binds selectively to GlcNAc-T V and has been used to visualize B-16 mouse melanoma cell GlcNAc-T V on immunoblots after SDS-PAGE. When the antisera was used in immunofluorescence microscopy experiments on permeabilized B-16 and baby hamster kidney cells, intense, specific staining was observed in intracellular structures which appear to correspond to the Golgi apparatus.
Animals↗