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PubMed1990

Activation of cyclic AMP phosphodiesterase by phorbol and protein kinase C pathway: differences in normal and diabetic tissue.

Diabetes mellitus is associated with high levels of adenosine 3',5'-cyclic monophosphate in tissue and plasma. Diabetes inhibits and insulin stimulates and restores low Km adenosine 3',5'-cyclic monophosphate phosphodiesterase activity. We recently reported that phorbol ester, a tumor promoting agent known to act through protein kinase C also stimulates phosphodiesterase. Here, we address the issue of whether or not the activation of phosphodiesterase by insulin and phorbol ester is different in streptozotocin diabetic adipose tissue. Rat adipose tissue was incubated with insulin, phorbol ester or other known components or effectors of the protein kinase C pathway, i.e. 1,2 dioleoyl-glycerol, 1- oleoyl, 2- acetylglycerol, Ca(++)-Ionophore A 23187, and nifedipine. After incubation, preparation and assay of adenosine 3',5'-cyclic monophosphate phosphodiesterase was made. As in previous data streptozotocin-diabetes inhibits basal phosphodiesterase by about 50% (P less than .02); insulin and phorbol ester each stimulate phosphodiesterase, in streptozotocin-diabetes less than normal (P less than .025); nifedipine inhibits phorbol stimulated phosphodiesterase in streptozotocin-diabetes but not normal (P less than .001); and nifedipine inhibits insulin stimulated phosphodiesterase in normal (84%) and diabetic (97%) (P less than .005). In normal and diabetic tissue, diacyl glycerol and oleoyl-acyl glycerol stimulate phosphodiesterase, are augmented by ionophore and inhibited by nifedipine. In addition 32P incorporation studies and measurements of tyrosine kinase activity are presented which support these differences between normal and diabetic. In summary then, these data suggest common pathways of activation for low Km adenosine 3',5'-cyclic monophosphate phosphodiesterase by insulin and phorbol ester; imply a relationship between two second messenger systems, phosphoinositides and adenosine 3',5'-cyclic monophosphate; and demonstrate a difference in activation of phosphodiesterase between normal and diabetic adipose tissue.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2006

Childhood death auditing to improve paediatric care.

AIM: Field-testing a paediatric mortality audit system at eight sites in South Africa to assess its feasibility, to collect local data on common causes of death in children under 5 y, and to determine health system failure, missed opportunities of intervention and substandard care (modifiable factors). METHODS: The study tested the Under-5 Healthcare Problem Identification Programme (U5PIP). The sites represent different levels of paediatric healthcare. STUDY PERIOD: 1 September 2003-31 August 2004. STUDY POPULATION: Under-5 patients admitted to study hospitals. CASES: Under-5 patients who died in study hospitals. RESULTS: In total, 1532 under-5 deaths occurred, representing a case-fatality rate of 7.8%. Main causes of death were lower respiratory tract infections (33%), gastroenteritis (15%) and septicaemia (12%). Sixty per cent of the deaths were HIV/AIDS related. Sixty-nine per cent of children who died were underweight. Administrative modifiable factors were present in 31% of deaths. Clinical personnel-related modifiable factors were detected in 26% at the clinic level and in 33-37% at the hospital level. CONCLUSION: The U5PIP is feasible for ongoing mortality reviews by paediatric teams as part of routine work. Information on common causes of death and modifiable factors in this study focus on the impact of HIV/AIDS, malnutrition and resource allocation, and can be used for interventions to improve paediatric healthcare.

Cause of Death↗

PubMed2005

General health status of residents of the Selebi Phikwe Ni-Cu mine area, Botswana.

Residents of the Selebi Phikwe area, Botswana where nickel-copper (Ni-Cu) is being exploited often exhibit symptoms of varied degrees of ailments, sicknesses and diseases. A need to investigate their general health status was therefore eminent. Primary data was obtained by means of a questionnaire and structured interviews conducted with individuals, health service providers, business enterprises and educational Institutions. The generated data revealed common ailments, sicknesses and diseases in the area with the four most frequent health complaints being frequent coughing headaches, influenza/common colds and rampant chest pains. Research findings indicated that residents had respiratory tract-related problems, suspected to be linked to the effects of air pollution caused by the emission of sulphur dioxide (SO2) from mining and smelting activities. Residents were frequently in contact with SO2 and related gases and fumes, mineral and silica dust generated from the mining processes. No clearly demarcating differences were noticed in the health status of residents living in the control site from those in the main study area. However, sites most affected were those close to where Ni-Cu is exploited. Environmental factors resulting from mining and smelting activities, among others, could be contributory to the negative health effects occurring at Selebi Phikwe.

Air Pollutants↗

PubMed2005

Individual and setting differences in the hand preferences of chimpanzees (Pan troglodytes): a critical analysis and some alternative explanations.

Several recent papers have been critical at a theoretical and empirical level of the evidence of population-level right-handedness in chimpanzees and other great apes. For example, Palmer (2002) has recently argued that the evidence of population-level handedness in chimpanzees is weak because there are sampling biases in the data. McGrew and Marchant (1997) argue that all the evidence of right-handedness in apes is from captive animals and therefore the observed phenomenon has little ecological validity. In this paper, we address recent issues regarding the presentation and interpretation of other hand preference data and argue that chimpanzees are right-handed for some measures. We further argue that purported differences in hand use between wild and captive chimpanzees due to rearing environments are unfounded and we emphasise that more cooperative work between researchers working in captive and feral populations is needed to facilitate collection of data on common measures of hand preference.

Animals↗

PubMed2006

IQ-based norms for highly intelligent adults.

This study presents normative data of commonly used neuropsychological tests administered to 75 individuals with high levels of intelligence (estimated IQ > or = 120). Participants were living independently in the community with ages ranging from 44 to 86. To avoid including individuals with an incipient dementia, we selected subjects who scored within the normal range on all cognitive tests for at least a two-year period. The norms are presented in table format to help clinicians easily identify a typical cognitive performance in highly intelligent individuals and to provide a useful guide for detecting abnormal cognitive decline in individuals at risk for progressive dementia.

Adult↗

PubMed2002

Five-year mortality for stable angina in a medical practice study and a randomized trial.

OBJECTIVE: Evolution of revascularization and medical therapy has increased the probability of improved survival in patients with stable angina. The present investigation tests the hypothesis that medical practice will generate lower mortality than randomly assigned bypass surgery in the European Coronary Surgery Study (ECSS) two decades earlier. METHOD: Using eligibility criteria of ECSS, a clinical decision strategy (CDS) cohort of 362 patients was selected from a nationwide study of medical practice in Sweden. Access to the individual data allowed common protocol design to compare 5-year mortality between CDS and surgical strategy of ECSS. RESULTS AND INTERPRETATION: CDS advised bypass surgery (BS) or percutaneous transluminal coronary angioplasty (PTCA) in 93% and medical treatment alone in 7%, while 94% of 394 patients randomized to surgery (Euro-S) in ECSS obtained BS. Operative mortality was 3.2% for Euro-S while no operative deaths occurred in CDS reflecting medical progress during two decades. However, the 5-year mortality for CDS decreased first when the risk ratio was adjusted for age, diabetes mellitus and hypertension (RR = 0.49 with 95% CI 0.26-0.93) p = 0.03 suggesting a need for improved comprehensive medical care.

Angina Pectoris↗

PubMed2004

Frailty models for quality of life in oncology.

Quality of life (QOL) and survival data are commonly measured in clinical trials in oncology. Frailty models are an excellent tool to exploit the natural dependence between these domains. We propose a novel application of frailty models, providing a detailed example relating to QOL in advanced prostate cancer patients. We discuss model fitting, estimation, and interpretation and describe available software.

Clinical Trials, Phase III as Topic↗

PubMedDate not supplied

Seasonal use of torpor by free-ranging Australian owlet-nightjars (Aegotheles cristatus).

With the exception of some data for common poorwills (Phalaenoptilus nuttallii) and anecdotal reports for a few other species, knowledge about the use of torpor by free-ranging birds is limited. Our study was designed to assess the use of torpor by free-ranging Australian owlet-nightjars (Aegotheles cristatus). We selected this species for study because of their relatively small body size (50 g), arthropod diet, nocturnal sedentary nature, taxonomic affiliation with other birds for whom the use of torpor is well documented, use of cavity roosts, and because of the cold winter (mean July minimum ambient temperature [T(a)] of approximately 0 degrees C) in the study area. We tracked 12 owlet-nightjars carrying temperature-sensitive transmitters for a total of 906 bird-days (range of 15-115 d per individual). Five different individuals entered torpor on 96 d in total. Torpor bouts occurred only between May 8 and September 8, the coldest period of the year. The lowest skin temperature (T(skin)) recorded for any bird was 19.6 degrees C, and the lowest core temperature was 22.4 degrees C. Surprisingly, torpor was rarely used at night because birds usually foraged then. Instead, torpor typically began near dawn, even on cold nights. Torpor bouts beginning at dawn lasted approximately 4 h. On 36% of days when torpor was used at dawn, birds reentered torpor later in the day. Torpor was not used during the breeding season, but this period also corresponds to the warm part of the year. There were no distinct daily minimum, maximum, or mean T(a) thresholds that could be used to reliably distinguish days when dawn torpor was used from those when it was not, although torpor was commonly employed when daily minimum T(a) fell below 3.9 degrees C. Our results show that even though Australia is typically thought of as a warm continent, at least some of the avifauna use torpor as a regular means of saving energy. We hypothesise that the reasons for this species' use of torpor include its ability to remain active all night foraging, either for terrestrial arthropods while walking or for flying insects taken on the wing, and/or its habit of roosting in cavities, which allows them to remain hidden in the daytime.

Adaptation, Physiological↗

PubMed2004

Two drugs or three? Balancing efficacy, toxicity, and resistance in postexposure prophylaxis for occupational exposure to HIV.

Thousands of health care workers are potentially exposed to human immunodeficiency virus (HIV) each year via occupationally acquired needlesticks. The Centers for Disease Control and Prevention (Atlanta, GA) advise health care workers who experience a high-risk occupational exposure from an HIV-infected patient to begin receiving multidrug antiretroviral postexposure prophylaxis (PEP) as soon as possible, preferably within 36 h after exposure. Although the need to prescribe antiretroviral postexposure prophylaxis in a timely fashion is common, few data exist regarding the efficacy and optimal regimen for prophylaxis to prevent transmission. Our objectives were to examine the limited human and animal data on postexposure prophylaxis, to elucidate the factors that affect the choice of 2 versus 3 drugs as the optimal prophylactic drug regimen, and to place these findings within a mathematical framework to help guide the prescription of PEP.

Animals↗

PubMed2004

Longitudinal risk of herpes simplex virus (HSV) type 1, HSV type 2, and cytomegalovirus infections among young adolescent girls.

BACKGROUND: Cross-sectional seroprevalence studies indicate that infections with herpes simplex virus (HSV) types 1 (HSV-1) and 2 (HSV-2) and cytomegalovirus (CMV) are common. However, data on the rates of acquisition of these infections are limited. METHODS: A 3-year longitudinal study of HSV-1, HSV-2, and CMV seroprevalence was conducted in a cohort of 174 adolescent girls (age at enrollment, 12-15 years). RESULTS: At study entry, 41% of the girls reported a history of sexual activity, and by the end of the study, 73% reported a history of sexual activity. At enrollment, 71% of all participants were seropositive for CMV, 44% were seropositive for HSV-1, and 7% were seropositive for HSV-2. By the end of the study, 81% of the girls were seropositive for CMV, 49% were seropositive for HSV-1, and 14% were seropositive for HSV-2. Among girls with a history of sexual activity, 15.5% were HSV-2 seropositive at the beginning of the study, and 18.9% were HSV-2 seropositive at the end of the study. The attack rates, based on the number of cases per 100 person-years, were 13.8 for CMV infection and 3.2 for HSV-1 infection (among all girls) and 4.4 for HSV-2 infection (among girls with a history of sexual activity). Participants with preexisting HSV-1 antibodies were associated with a significantly lower attack rate for HSV-2 infection. A generalized estimating equation model indicated that participants with a longer history of sexual activity and those who had more sexually transmitted diseases during the 6-month periods before the study visits were more likely to be HSV-2 seropositive. CONCLUSIONS: This longitudinal study of adolescent girls found high baseline CMV and HSV-1 seroprevalence rates and substantial attack rates for all 3 pathogens.

Adolescent↗

PubMed2004

Fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae from Asian countries: ANSORP study.

Seventeen clinical isolates of Streptococcus pneumoniae showing reduced susceptibility to ciprofloxacin (MIC >/= 4 micro g/ml) collected from eight different Asian countries were analyzed by antimicrobial susceptibility, serotyping, pulsed-field gel electrophoresis (PFGE), and DNA sequencing of the quinolone resistance-determining regions (QRDRs) in gyrA, gyrB, parC, and parE. All isolates but one showed more than one amino acid alteration in QRDRs of four responsible genes. Ile460 --> Val in parE was the most common mutation. Data suggest that Lys137 --> Asn in parC may be a primary step in the development of high-level and multiple FQ resistance. An additional mutation of Ser81 --> Phe in gyrA resulted in high-level resistance to ciprofloxacin, levofloxacin, and gatifloxacin, whereas Ser79 --> Phe in parC may exert an important role in the development of moxifloxacin resistance. Two novel amino acid changes in gyrB, Ala390 --> Val and Asn423 --> Thr, were found. Data from PFGE suggest an introduction and local spread of multiple resistant Spain(23F)-1 clone in Hong Kong, but isolates from other Asian countries were not related to this clone.

Anti-Bacterial Agents↗

PubMed1994

Protein secondary structure prediction using two-level case-based reasoning.

We have developed a two-level case-based reasoning architecture for predicting protein secondary structure. The central idea is to break the problem into two levels: (i) reasoning at the object (protein) level and using the global information from this level to focus on a more restricted problem space; (ii) decomposing objects into pieces (segments) and reasoning at the level of internal structures. As a last step to the procedure, inferences from the parts of the internal structure are synthesized into predictions about global structure. The architecture has been developed and tested on a commonly used data set with 69.5% predictive accuracy. It was then tested on a new data set with 68.2% accuracy. With additional tuning, over 70% accuracy was achieved. In addition, a series of experiments were conducted to test various aspects of the method and the results are informative.

Amino Acid Sequence↗

PubMed2003

Estimating the relative risk in cohort studies and clinical trials of common outcomes.

Logistic regression yields an adjusted odds ratio that approximates the adjusted relative risk when disease incidence is rare (<10%), while adjusting for potential confounders. For more common outcomes, the odds ratio always overstates the relative risk, sometimes dramatically. The purpose of this paper is to discuss the incorrect application of a proposed method to estimate an adjusted relative risk from an adjusted odds ratio, which has quickly gained popularity in medical and public health research, and to describe alternative statistical methods for estimating an adjusted relative risk when the outcome is common. Hypothetical data are used to illustrate statistical methods with readily accessible computer software.

Clinical Trials as Topic↗

PubMed2006

Sibship characteristics and risk of multiple sclerosis: a nationwide cohort study in Denmark.

It has been hypothesized that age at infection with a common microbial agent may be associated with the risk of multiple sclerosis (MS). The authors addressed this hypothesis by using number of older siblings and other sibship characteristics as an approximation of age at exposure to common infections. Data on family characteristics and vital status from the Danish Civil Registration System were used to establish a cohort of all Danes whose mothers had been born in Denmark since 1935. Persons diagnosed with MS during the period 1968-1998 were identified through linkage with the Danish Multiple Sclerosis Register. The cohort of 1.9 million Danes was followed for 28.1 million person-years; during that time, 1,036 persons developed MS. Overall, there was no association between number of older siblings, number of younger siblings, total number of siblings, age distance from the nearest younger sibling, or exposure to younger siblings under 2 years of age and risk of MS later in life. There was no association of MS risk with multiple birth (vs. singleton birth) or with the age of the mother or father at birth. These results do not lend support to the hypothesis that number of older siblings or any of the other sibship characteristics studied is associated with risk of MS.

Adolescent↗

PubMed2005

Occupational and environmental factors and idiopathic pulmonary fibrosis in Japan.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown etiology. Environmental factors, especially occupational agents, may be of great importance in the manifestation of IPF. We examined the relationship between occupational and environmental factors and IPF in Japan. A multicenter hospital-based case-control study was performed in 2001. Included were 102 cases aged 40 years or over who were within 2 years of having been diagnosed in accordance with the most recent criteria. Controls, aged 40 years or over, were 55 hospitalized patients diagnosed as having acute bacterial pneumonia and four outpatients with common colds. Data on occupational and environmental factors were obtained from a questionnaire. Multiple logistic regression analysis was used to estimate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of IPF for single factors with adjustment for age, sex and region. Compared with controls, cases were more likely to have been managers, officials or production workers and less likely to have been protective service or materials handling workers. Clerical and related work was significantly related to a decreased risk of IPF after further adjustment for pack-years of smoking (OR = 0.42; 95% CI = 0.18-0.95). Exposure to metal dust was significantly associated with an increased risk of IPF (OR = 9.55; 95% CI = 1.68-181.12). From 20.0 to 39.9 pack-years of smoking was significantly associated with an increased risk of IPF (OR = 3.23; 95% CI = 1.01-10.84). Our results appear to confirm data from previous epidemiologic studies. Metal dust exposure may be a particularly important risk factor for IPF.

Adult↗

PubMed1992

International Database on Hodgkin's Disease: a cooperative effort to determine treatment outcome.

In an effort to better determine the outcome of patients treated for Hodgkin's disease, twenty institutions/cooperative groups in the western world agreed in 1988 to participate in the development of a large data base by sending data to be analyzed by a common statistical design. Data was obtained from both patients randomized on prospective trials and patients treated by standard protocol but not randomized. Overall statistics on 14,315 adult patients treated from the early 1960s to 1987 were collected. This data was first presented at the Paris International Workshop and Symposium held on June 28-30, 1989. The proceedings, published in 1990, include a detailed description of the data, and prognostic studies on laparotomy findings, response to initial therapy, relapse-free survival, overall survival, and secondary malignancies. The International Database on Hodgkin's Disease represents a compromise between two more classical approaches such as the use of randomized trials and metaanalyses. It should serve as a model for the study of other types of cancer. It has been successful because of interest, time, and the cooperation of physicians in academic centers from much of the western world.

Databases, Factual↗

PubMed2003

Structure of the developing pea seed coat and the post-phloem transport pathway of nutrients.

An important function of the seed coat is to deliver nutrients to the embryo. To relate this function to anatomical characteristics, the developing seed coat of pea (Pisum sativum L.) was examined by light- and cryo-scanning electron microscopy (cryo-SEM) from the late pre-storage phase until the end of seed filling. During this time the apparently undifferentiated seed coat tissues evolve into the epidermal macrosclereids, the hypodermal hourglass cells, chlorenchyma, ground parenchyma and branched parenchyma. Using the fluorescent symplast tracer 8-hydroxypyrene-1,3,6-trisulfonic acid, it could be demonstrated that solutes imported by the phloem move into the chlorenchyma and ground parenchyma, but not into the branched parenchyma. From a comparison with literature data of common bean (Phaseolus vulgaris L.) and broad bean (Vicia faba L.), it is concluded that in the three species different parenchyma layers, but not the branched parenchyma, may be involved in the post-phloem symplasmic transport of nutrients in the seed coat. In pea, the branched parenchyma dies during the storage phase, and its cell wall remnants then form the boundary layer between the living seed coat parenchyma cells and the cotyledons. Using cryo-SEM, clear images were obtained of this boundary layer which showed that many intracellular spaces in the seed coat parenchyma are filled with an aqueous solution. This is suggested to facilitate the diffusion of nutrients from the site of unloading towards the cotyledons.

Arylsulfonates↗

PubMed2004

HIVbase: a PC/Windows-based software offering storage and querying power for locally held HIV-1 genetic, experimental and clinical data.

BACKGROUND: Human immunodeficiency virus (HIV) research involves ongoing, repetitious sequencing of the HIV genome and the massive accumulation of associated investigational data. As a result, the storage of annotated DNA and/or protein sequences, as well as information retrieval, have become increasingly difficult tasks, with scientists extracting less information from their collected data than they should. OBJECTIVES: Our objective was to design and develop a software package to aid researchers in the storage, analysis and exploration of their HIV-associated data. RESULTS: HIVbase contains familiar, easy-to-use interfaces and functionality for integrating many types of disparate data. The software contains tools that allow for the mass import of raw genetic data, eliminate repetitious sequence translations, have the ability to identify automatically and store HIV regions of interest from nucleic acid or protein sequences, allow for the export of data in commonly used analysis-ready formats, and for unique querying approaches.

Algorithms↗