Biomedical subjects

J Ziegler

Publications and source records attributed to J Ziegler.

At least 19 recordsLinked to original sources

PubMed2004

Human papillomaviruses and cancer in Uganda.

In a case-control study in Uganda, we examined associations between different cancer sites or types in relation to antibodies against human papillomaviruses (HPV)-16, -18 and -45. For each cancer site or type, the control group comprised all other cancers excluding those known, or thought to be associated with HPV infection (cancers of the uterine cervix, penis and eye). Among controls the seroprevalence of antibodies was 11% (68/616) against HPV-16, 5% (29/605) against HPV-18 and 6% (35/605) against HPV-45. Antibodies against HPV-16 were significantly associated with only two cancers: uterine cervix [prevalence of antibodies 27% (51/191); odds ratio (OR) 2.0, 95% confidence interval (CI) 1.2-3.1, P=0.01] and penis [prevalence of antibodies 27% (4/15); OR 6.4, 95% CI 1.7-24.3, P=0.01]. For both cancers, the risk increased with increasing anti-HPV-16 antibody titre (Ptrend=0.01 for each). No cancer site or type was significantly associated with antibodies against HPV-18 and -45.

Adult↗

PubMed2004

ASCIA guidelines for prevention of food anaphylactic reactions in schools, preschools and child-care centres.

These guidelines have been developed by the anaphylaxis working party of the Australasian Society of Clinical Immunology and Allergy to provide advice for minimizing the risk of food-induced anaphylaxis in schools, preschools and child-care centres. The guidelines outline four steps for the prevention of food anaphylactic reactions in children at risk and food policy measures specific to school age and preschool age children.

Age Factors↗

PubMed2003

Infection with Kaposi's sarcoma-associated herpesvirus (KSHV) and human immunodeficiency virus (HIV) in relation to the risk and clinical presentation of Kaposi's sarcoma in Uganda.

A case-control study from Uganda found that the risk of Kaposi's sarcoma increased with increasing titre of antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV) latent nuclear antigens, independently of HIV infection. Clinically, widespread Kaposi's sarcoma was more frequent among patients with HIV infection than in those without, but was not related to anti-KSHV antibody titres.

Adolescent↗

PubMed2002

The epidemiology of conjunctival squamous cell carcinoma in Uganda.

As part of a larger investigation of cancer in Uganda, we conducted a case-control study of conjunctival squamous cell carcinoma in adults presenting at hospitals in Kampala. Participants were interviewed about social and lifestyle factors and had blood tested for antibodies to HIV, KSHV and HPV-16, -18 and -45. The odds of each factor among 60 people with conjunctival cancer was compared to that among 1214 controls with other cancer sites or types, using odds ratios, estimated with unconditional logistic regression. Conjunctival cancer was associated with HIV infection (OR 10.1, 95% confidence intervals [CI] 5.2-19.4; P<0.001), and was less common in those with a higher personal income (OR=0.4, 95% CI 0.3-0.7; P<0.001)[corrected]. The risk of conjunctival cancer increased with increasing time spent in cultivation and therefore in direct sunlight (chi2 trend=3.9, P=0.05), but decreased with decreasing age at leaving home (chi2 trend=3.9, P=0.05), perhaps reflecting less exposure to sunlight consequent to working in towns, although both results were of borderline statistical significance. To reduce confounding, sexual and reproductive variables were examined among HIV seropositive individuals only. Cases were more likely than controls to report that they had given or received gifts for sex (OR 3.5, 95% CI 1.2-10.4; P=0.03), but this may have been a chance finding as no other sexual or reproductive variable was associated with conjunctival cancer, including the number of self-reported lifetime sexual partners (P=0.4). The seroprevalence of antibodies against HPV-18 and -45 was too low to make reliable conclusions. The presence of anti-HPV-16 antibodies was not significantly associated with squamous cell carcinoma of the conjunctiva (OR 1.5, 95% CI 0.5-4.3; P=0.5) and nor were anti-KSHV antibodies (OR 0.9, 95% CI 0.4-2.1; P=0.8). The 10-fold increased risk of conjunctival cancer in HIV infected individuals is similar to results from other studies. The role of other oncogenic viral infections is unclear.

Adolescent↗

PubMed2002

Adsorption and release properties of growth factors from biodegradable implants.

The present investigation was performed to study the adsorption behavior of growth factors and their release characteristics from biodegradable implants in an in vitro study. We investigated the stability of growth factors administered on various scaffolds. We used porous tricalcium phosphate ceramics (alpha-TCP), a neutralized glass-ceramics (GB9N), a composite (polylactid/-glycolid/GB9N), and solvent dehydrated human bone as carriers. Block shaped scaffolds (sized: 7 x 7 x 10 mm) were loaded with 5 microg of either bone morphogenetic protein (rxBMP-4), basic fibroblast growth factor (rh-bFGF), or vascular endothelial growth factor (rh-VEGF) solved in 150 microL PBS. The growth factors were labeled with Iodine125 (I-125) for detecting the adsorbed and released amount of growth factors by counting the samples for total I-125 activity. We observed that the adsorption of these growth factors seems to depend on two different parameters: first on the nature of the tested material, and second on the growth factors on their own. The release kinetics of the growth factors from the biodegradable implants can be described as a two phase process-a very rapid release during the first hours by an elution of not adsorbed protein, followed by a specific release, which depends upon the chemical/physical interaction of the material and the growth factor used. Analyzing the eluted proteins on SDS-PAGEs rh-VEGF was degraded into a smaller fragment with a size of around 15 kDa, while rxBMP-4 and rh-bFGF showed a complete degradation into fragments smaller than 3 kDa after more than 3 days. Although this in vitro study suggests that biodegradable implants might be successfully used as carriers for osteogenic growth factors, the different release kinetics as well as the alteration of their molecular structure including loss of biological activity should be considered.

Absorbable Implants↗

PubMed2002

Topical calcipotriol plus oral fumaric acid is more effective and faster acting than oral fumaric acid monotherapy in the treatment of severe chronic plaque psoriasis vulgaris.

BACKGROUND: Calcipotriol is an established topical therapy for psoriasis vulgaris. OBJECTIVE: This study aimed to investigate whether the addition of calcipotriol to fumaric acid ester (FAE) monotherapy had an additive efficacy and an FAE-sparing effect in patients with severe plaque psoriasis. METHODS: This multicentre, randomised, double-blind, vehicle-controlled study included 143 patients for up to 13 weeks treatment. Group A received FAE tablets (Fumaderm) with an increasing daily dosage from 105 to 1,075 mg + ointment vehicle. Group B received FAE tablets + calcipotriol ointment (50 microg/g). Ointments were applied twice daily. Clinical response was assessed using percentage changes in the Psoriasis Area and Severity Index (PASI), from baseline to treatment end. RESULTS: The mean percentage change in the PASI was -76.1% in group B and -51.9% in group A, the difference between treatments was -24.2% (95% CI from -34.2 to -14.2%; p < 0.001). Group B responded more rapidly to treatment. Investigators' and patients' overall efficacy assessments were significantly more favourable for group B (p < or = 0.001). Group B was prescribed less FAE than group A. This difference was greatest at the last visit (mean daily dose 529 and 685 mg, respectively; p = 0.006). Overall adverse events in the two groups were similar. CONCLUSION: This study shows that the combination of calcipotriol and FAEs is significantly more effective and faster acting than FAE monotherapy in the treatment of severe plaque psoriasis. The combination has a slight FEA-sparing effect and therefore a superior benefit/risk ratio.

Administration, Oral↗

PubMed2001

A case-control study of human immunodeficiency virus infection and cancer in adults and children residing in Kampala, Uganda.

Uganda offers a unique setting in which to study the effect of human immunodeficiency virus-1 (HIV-1) on cancer. HIV-1 is prevalent there, and cancers which are known to be HIV-associated, such as Kaposi's sarcoma and Burkitt's lymphoma, are endemic. Adults residing in Kampala, Uganda, presenting with cancer in city hospitals were interviewed and had an HIV test. Of the 302 adults recruited, 190 had cancers with a potentially infectious aetiology (cases). The remaining 112 adults with tumours not known to have an infectious aetiology formed the control group. In addition, 318 children who were also Kampala residents were recruited and tested for HIV: 128 with cancer (cases) and 190 with non-malignant conditions (controls). HIV seroprevalence was 24% in adult controls and 6% in childhood controls. The odds of HIV seropositivity among cases with specific cancers (other than Kaposi's sarcoma in adults) were compared with that among controls, using odds ratios (ORs), estimated with unconditional logistic regression. All ORs were adjusted for age (<5, 5-14, 15-19, 30-44, 45+) and sex and, in adults, also for the number of lifetime sexual partners (1 or 2, 3-9, 10+). In adults, HIV infection was associated with a significantly (p < 0.05) increased risk of non-Hodgkin's lymphoma [OR = 6.2, 95% confidence interval (CI) 1.9-19.9, based on 21 cases] and conjunctival squamous-cell carcinoma (OR = 10.9, 95% CI 3.1-37.7, based on 22 cases) but not with cancer at other common sites, including liver and uterine cervix. In children, HIV infection was associated with a significantly increased risk of Kaposi's sarcoma (OR = 94.9, 95% CI 28.5-315.3, based on 36 cases) and Burkitt's lymphoma (OR = 7.5, 95% CI 2.8-20.1, based on 33 cases) but not with other cancers. The pattern of HIV-associated cancers in Uganda is broadly similar to that described elsewhere, but the relative frequency of specific cancers, such as conjunctival carcinoma, in HIV-infected people differs.

Adolescent↗

PubMed2001

Herbivore-induced allene oxide synthase transcripts and jasmonic acid in Nicotiana attenuata.

Exogenous jasmonate treatment of Nicotiana attenuata Torr. ex Wats. plants elicits durable resistance against herbivores and attack from its specialist herbivore, Manduca sexta, results in an amplification of the transient wound-induced increase in endogenous jasmonic acid levels (JA). To understand whether this "JA burst" is under transcriptional control, we cloned allene oxide synthase (AOS; EC 4.2.1.92), the enzyme that catalyzes the dehydration of 13(S)-hydroperoxy octadecatrienoic acid to an allene oxide, the first specific reaction in JA biosynthesis. An AOS cDNA coding for a 520 aa protein (58.6 kDa) with an isoelectric point of 8.74 was overexpressed in bacteria and determined to be a functional AOS. Southern blot analysis indicated the presence of more than one gene and AOS transcripts were detected in all organs, with the highest levels in stems, stem leaves and flowers. Attack by M. sexta larvae resulted in a sustained JA burst producing an endogenous JA amount 9-fold above control levels and 3-fold above maximum wound-induced levels, a response which could be mimicked by the addition of Manduca oral secretion and regurgitant to puncture wounds. M. sexta attack, wounding and regurgitant treatment transiently increased AOS transcript in the wounded leaf, but increases were not proportional to the JA response. Moreover, transcript accumulation lagged behind JA accumulation. Systemic wound-induced increases in AOS transcript, AOS activity or JA accumulation could not be detected. We conclude that increase in AOS transcript does not contribute to the initial increase in endogenous JA, but may contribute to sustaining the JA burst.

Amino Acid Sequence↗

PubMed2001

DRC: a dual route cascaded model of visual word recognition and reading aloud.

This article describes the Dual Route Cascaded (DRC) model, a computational model of visual word recognition and reading aloud. The DRC is a computational realization of the dual-route theory of reading, and is the only computational model of reading that can perform the 2 tasks most commonly used to study reading: lexical decision and reading aloud. For both tasks, the authors show that a wide variety of variables that influence human latencies influence the DRC model's latencies in exactly the same way. The DRC model simulates a number of such effects that other computational models of reading do not, but there appear to be no effects that any other current computational model of reading can simulate but that the DRC model cannot. The authors conclude that the DRC model is the most successful of the existing computational models of reading.

Dyslexia↗

PubMed2001

Evolving control metabolisms for a robot.

This article demonstrates a new method of programming artificial chemistries. It uses the emerging capabilities of the system's dynamics for information-processing purposes. By evolution of metabolisms that act as control programs for a small robot one achieves the adaptation of the internal metabolic pathways as well as the selection of the most relevant available exteroceptors. The underlying artificial chemistry evolves efficient information-processing pathways with most benefit for the desired task, robot navigation. The results show certain relations to such biological systems as motile bacteria.

Metabolism↗

PubMed2001

Artificial chemistries--a review.

This article reviews the growing body of scientific work in artificial chemistry. First, common motivations and fundamental concepts are introduced. Second, current research activities are discussed along three application dimensions: modeling, information processing, and optimization. Finally, common phenomena among the different systems are summarized. It is argued here that artificial chemistries are "the right stuff" for the study of prebiotic and biochemical evolution, and they provide a productive framework for questions regarding the origin and evolution of organizations in general. Furthermore, artificial chemistries have a broad application range of practical problems, as shown in this review.

Chemistry↗

PubMed2001

Heme Aggregation inhibitors: antimalarial drugs targeting an essential biomineralization process.

Malaria, resulting from the parasites of the genus Plasmodium, places an untold burden on the global population. As recently as 40 years ago, only 10% of the world's population was at risk from malaria. Today, over 40% of the world's population is at risk. Due to increased parasite resistance to traditional drugs and vector resistance to insecticides, malaria is once again resurgent. An emergent theme from current strategies for the development of new antimalarials is that metal homeostasis within the parasite represents an important drug target. During the intra-erythrocytic phase of its life cycle, the malaria parasite can degrade up to 75% of an infected cell's hemoglobin. While hemoglobin proteolysis yields requisite amino acids, it also releases toxic free heme (Fe(III)PPIX). To balance the metabolic requirements for amino acids against the toxic effects of heme, malaria parasites have evolved a detoxification mechanism which involves the formation of a crystalline heme aggregate known as hemozoin. An overview of the biochemistry of the critical detoxification process will place it in the appropriate context with regards to drug targeting and design. Quinoline-ring antimalarial drugs are effective against the intraerythrocytic stages of pigment-producing parasites. Recent work on the mechanism of these compounds suggests that they prevent the formation of hemozoin. Evidence for such a mechanism is reviewed, especially in the context of the newly reported crystal structure of hemozoin. Additionally, novel drugs, such as the hydroxyxanthones, which have many of the characteristics of the quinolines are currently being investigated. Recent work has also highlighted two classes of inorganic complexes that have interesting antimalarial activity: (1) metal-N(4)O(2) Schiff base complexes and (2) porphyrins. The mechanism of action for these complexes is discussed. The use of these complexes as probes for the elucidation of structure-activity relationships in heme polymerization inhibitor design and the loci of drug resistance is also detailed. As the biochemistry of the complicated interactions between host, parasite, and vector become better understood, the rationale for new antimalarial drug treatments will continue to improve. Clearly, the homeostasis of metal ions is a complicated biochemical process and is not completely understood. For the immediate future, it does, however, provide a clear target for the development of new and improved treatments for malaria.

Animals↗

PubMed2000

Non-Hodgkin lymphoma in Uganda: a case-control study.

BACKGROUND: Lymphomas are a relatively common complication of AIDS in western countries, but little is known of the impact of the AIDS epidemic in Africa on the risk of these tumours. OBJECTIVE: To investigate the types of non-Hodgkin lymphoma (NHL) occurring in Kampala, Uganda, their association with Epstein-Barr virus (EBV), and how their risk is modified by HIV and other variables. METHODS: A case-control study comparing NHL cases with age/sex-matched controls. Lymphoma cases included 50 histologically diagnosed adults (31 with validation and phenotyping) and 132 histologically diagnosed children (61 with validation and phenotyping). Controls were adults with cancers unrelated to HIV and children with non-infectious diseases. RESULTS: Most (90%) childhood lymphomas were EBV-positive Burkitt's lymphoma (BL), with no association with HIV. Adult lymphoma cases were mainly BL (mostly EBV positive) or diffuse B cell lymphomas (71%). Only a weak association was found with HIV infection; a more precise estimate was obtained with the total series (OR 2.2, 95% CI 0.9-5.1) than validated/phenotyped cases (OR 2.1, 95% CI 0.3-6.7). Higher socioeconomic status adults, who travelled away from home, or had a history of sexually transmitted diseases, appeared to have a moderately increased risk of lymphoma. CONCLUSION: Childhood lymphomas were predominantly endemic BL, the risk of which was not modified by HIV. In adults, the risk associated with HIV was much lower in Uganda than in western countries, possibly because of the poor survival of immunosuppressed HIV-positive individuals. Future studies will require careful attention to subtyping of lymphomas, to investigate the possible differences between them.

Adolescent↗

PubMed2000

Molecular cloning of allene oxide cyclase. The enzyme establishing the stereochemistry of octadecanoids and jasmonates.

Allene oxide cyclase (EC ) catalyzes the stereospecific cyclization of an unstable allene oxide to (9S,13S)-12-oxo-(10,15Z)-phytodienoic acid, the ultimate precursor of jasmonic acid. This dimeric enzyme has previously been purified, and two almost identical N-terminal peptides were found, suggesting allene oxide cyclase to be a homodimeric protein. Furthermore, the native protein was N-terminally processed. Using degenerate primers, a polymerase chain reaction fragment could be generated from tomato, which was further used to isolate a full-length cDNA clone of 1 kilobase pair coding for a protein of 245 amino acids with a molecular mass of 26 kDa. Whereas expression of the whole coding region failed to detect allene oxide cyclase activity, a 5'-truncated protein showed high activity, suggesting that additional amino acids impair the enzymatic function. Steric analysis of the 12-oxophytodienoic acid formed by the recombinant enzyme revealed exclusive (>99%) formation of the 9S,13S enantiomer. Exclusive formation of this enantiomer was also found in wounded tomato leaves. Southern analysis and genetic mapping revealed the existence of a single gene for allene oxide cyclase located on chromosome 2 of tomato. Inspection of the N terminus revealed the presence of a chloroplastic transit peptide, and the location of allene oxide cyclase protein in that compartment could be shown by immunohistochemical methods. Concomitant with the jasmonate levels, the accumulation of allene oxide cyclase mRNA was transiently induced after wounding of tomato leaves.

Amino Acid Sequence↗

PubMed2000

Metalloporphyrins inhibit beta-hematin (hemozoin) formation.

Metal-substituted protoporphyrin IXs (Cr(III)PPIX (1), Co(III)PPIX (2), Mn(III)PPIX (3), Cu(II)PPIX (4), Mg(II)PPIX (5), Zn(II)PPIX (6), and Sn(IV)PPIX (7)) act as inhibitors to beta-hematin (hemozoin) formation, a critical detoxification biopolymer of malarial parasites. The central metal ion plays a significant role in the efficacy of the metalloprotoporphyrins to inhibit beta-hematin formation. The efficacy of these compounds correlates well with the water exchange rate for the octahedral aqua complexes of the porphyrin's central metal ion. Under these in vitro reaction conditions, metalloporphyrins 5, 6 and 7 are as much as six times more efficacious than the free ligand protoporphyrin IX in preventing beta-hematin formation and four times as efficacious as chloroquine, while metalloporphyrins 3 and 4 are three to four times more effective at preventing beta-hematin formation than the free protoporphyrin IX base. In contrast, the relatively exchange inert metalloporphyrins 1 and 2 are only as efficacious as the free ligand and only two-thirds as effective as chloroquine. Aggregation studies of the heme:MPPIX using UV-Vis and fluorescence spectroscopies are indicative of the formation of pi-pi hetero-metalloporphyrin assemblies. Thus, hemozoin inhibition is likely prevented by the formation of heme:MPPIX complexes through pi-stacking interactions. The ramifications of such hetero-metalloporphyrin assemblies, in the context of the emerging structural picture of hemozoin, are discussed.

Hemeproteins↗

PubMed2000

Allene oxide synthases of barley (Hordeum vulgare cv. Salome): tissue specific regulation in seedling development.

Allene oxide synthase (AOS) is the first enzyme in the lipoxygenase (LOX) pathway which leads to formation of jasmonic acid (JA). Two full-length cDNAs of AOS designated as AOS1 and AOS2, respectively, were isolated from barley (H. vulgare cv. Salome) leaves, which represent the first AOS clones from a monocotyledonous species. For AOS1, the open reading frame encompasses 1461 bp encoding a polypeptide of 487 amino acids with calculated molecular mass of 53.4 kDa and an isoelectric point of 9.3, whereas the corresponding data of AOS2 are 1443 bp, 480 amino acids, 52.7 kDa and 7.9. Southern blot analysis revealed at least two genes. Despite the lack of a putative chloroplast signal peptide in both sequences, the protein co-purified with chloroplasts and was localized within chloroplasts by immunocytochemical analysis. The barley AOSs, expressed in bacteria as active enzymes, catalyze the dehydration of LOX-derived 9- as well as 13-hydroperoxides of polyenoic fatty acids to the unstable allene oxides. In leaves, AOS mRNA accumulated upon treatment with jasmonates, octadecanoids and metabolizable carbohydrates, but not upon floating on abscisic acid, NaCl, Na-salicylate or infection with powdery mildew. In developing seedlings, AOS mRNA strongly accumulated in the scutellar nodule, but less in the leaf base. Both tissues exhibited elevated JA levels. In situ hybridizations revealed the preferential occurrence of AOS mRNA in parenchymatic cells surrounding the vascular bundles of the scutellar nodule and in the young convoluted leaves as well as within the first internode. The properties of both barley AOSs, their up-regulation of their mRNAs and their tissue specific expression suggest a role during seedling development and jasmonate biosynthesis.

Amino Acid Sequence↗

PubMed2000

Tissue-specific oxylipin signature of tomato flowers: allene oxide cyclase is highly expressed in distinct flower organs and vascular bundles.

A crucial step in the biosynthesis of jasmonic acid (JA) is the formation of its correct stereoisomeric precursor, cis(+)12-oxophytodienoic acid (OPDA). This step is catalysed by allene oxide cyclase (AOC), which has been recently cloned from tomato. In stems, young leaves and young flowers, AOC mRNA accumulates to a low level, contrasting with a high accumulation in flower buds, flower stalks and roots. The high levels of AOC mRNA and AOC protein in distinct flower organs correlate with high AOC activity, and with elevated levels of JA, OPDA and JA isoleucine conjugate. These compounds accumulate in flowers to levels of about 20 nmol g-1 fresh weight, which is two orders of magnitude higher than in leaves. In pistils, the level of OPDA is much higher than that of JA, whereas in flower stalks, the level of JA exceeds that of OPDA. In other flower tissues, the ratios among JA, OPDA and JA isoleucine conjugate differ remarkably, suggesting a tissue-specific oxylipin signature. Immunocytochemical analysis revealed the specific occurrence of the AOC protein in ovules, the transmission tissue of the style and in vascular bundles of receptacles, flower stalks, stems, petioles and roots. Based on the tissue-specific AOC expression and formation of JA, OPDA and JA amino acid conjugates, a possible role for these compounds in flower development is discussed in terms of their effect on sink-source relationships and plant defence reactions. Furthermore, the AOC expression in vascular bundles might play a role in the systemin-mediated wound response of tomato.

Cyclopentanes↗

PubMed2000

Differences in health values among patients, family members, and providers for outcomes in schizophrenia.

OBJECTIVE: The objectives of this study were to determine whether there are important differences in how patients, family members, and health care providers (HCPs) value health outcomes in schizophrenia and to assess the degree to which such differences, if they exist, could adversely affect clinical and policy decision making. METHODS: Participants viewed videotaped depictions of simulated patients with mild and moderate symptoms of schizophrenia, with and without a common adverse drug effect (pseudoparkinsonism), and then provided standard gamble and visual analog scale ratings of desirability of these states. SUBJECTS: A convenience sample of unrelated patients (n = 148), family members of patients (n = 91), and HCPs (nurses, psychologists, doctors of pharmacy, and doctors of medicine; n = 99) was drawn from geographically and clinically diverse environments. RESULTS: Patients' and family members' utilities for health states averaged 0.1 to 0.15 units higher than those of HCPs (P <0.002 for differences between groups, ANOVA for multiple observations). The disutility of adverse drug effects was less for health professionals than patients and family members (P = 0.008). Health professionals tended to prefer states with mild symptoms with extrapyramidal side effects to states with moderate symptoms. Patients and family members found these states equally preferable (P <0.007 for differences between groups). CONCLUSIONS: There are systematic differences in values for health outcomes between patients and HCPs with regard to states with adverse effects of antipsychotic drugs. Family members of patients in general had values that were more similar to those of patients than were those of health professionals. The results emphasize the importance of participation by patients (or family member proxies) in clinical decision making and guideline development.

Adult↗