8 research outputs found
Functional Response of Neutrophils in the Presence of LPS: Aspects of Locomotion and Metabolism in Normal and Diabetic Cells
No full textThis thesis reports a study of effects of bacterial lipopolysaccharides (LPS) on morphological polarization, locomotion and chemiluminescence of human neutrophi. leukocytes (polymorphonuclear leukocytes:PMN). Change from a spherical to a polarized morphology by a cell is the initial event in cell locomotion. PMN in suspension were shown to change shape even in the presence of small amounts of LPS (≥100 ng/ml) in the medium. Exposing PMN to LPS from rough strains of bacteria resulted in slow shape change (60-90 minutes), unlike chemotactic factors which cause shape change within a few minutes. This suggests an indirect effect. Rough strains were more active than the smooth chemotypes in inducing polarization of PMN. The number of polarized cells increased as the period of incubation increased implying the possible presence of a second (non-LPS) agonist that promoted further polarizing activity. Polymyxin B sulfate (10mug/ml) was added to the cells prior to challenging with LPS (10mug/ml) in order to inhibit this biological effect. However, polymyxin in this system did not reduce the number of polarized PMN to a statistically significant extent. To test if a chemotactic-type factor might have been released by the cells, supernatant was prepared from PMN (10e6 cells/ml) which had been incubated with LPS for 90 minutes. The supernatant (but not LPS alone) was shown to cause the shape change within 10 minutes in a shortterm polarization assay on a new batch of PMN. By reducing the cell density in the presence of constant amounts of LPS (10 mug/ml), it could be shown that polarizing activity of the supernatant was reduced. To assess the relationship of shape change to that of locomotory ability, three additional leukocyte locomotion assays were employed. With a micropore filter assay, migration of the cells in different concentration gradients of the factor showed that the released material behaved like a chemotactic factor as analyzed by the checkerboard system. A collagen gel assay was used to study detailed cell locomotion quantitatively (population of cells migrating) and also qualitatively (morphological changes during locomotion). Detailed behavioural analysis of the PMN response to LPS was obtained from visual studies. Quantitative measurements of shape change showed a slowly developing increase in elongation of the cells exposed to LPS for up to 90 minutes, in contrast to rapid elongation of cells exposed to the chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (FMLP). One of the ways a neutrophil might release a stimulant is through arachidonic acid metabolism. Steroidal and non-steroidal antiinflammatory drugs used to modulate the shape change process of the leukocytes displayed varied effects. Two drugs, with reported inhibitory effects on lipoxygenase activity, BW755C and Revlon 5901A reduced the number of PMN polarized by LPS. Conversely, neither indomethacin nor dexamethasone had any effect. Preliminary characterization of the cell released factor was also conducted. The factor was heat stable and non-dialyzable. Hexane extraction, thin layer chromatography and column gel filtration suggested that the released material was heterogenous. A low molecular weight factor (about 2000 kD) was identified by gel filtration on Sephadex G-25. Monoclonal antibodies against the CD11/CD18 family of cell surface receptors (shown by other researchers to be responsible for the binding of LPS to PMN) were used as inhibitors of LPS binding to PMN. Some antibodies were relatively effective in inhibiting LPS-induced PMN polarization particularly those against CD11b/CD18. Combinations of monoclonals against three antigens (CD11a, b and c) were more effective than any one alone. The study using these antibodies unexpectedly showed that the binding site of LPS to the phagocyte is highly affected by antibodies to the alpha-chain and not the beta-chain as reported by previous investigators. Competitive inhibitory binding of LPS to PMN was observed with synthetic peptides containing an RGD-sequence. The observation points to a probable involvement of the sequence in LPS-induced neutrophil polarization. Chemiluminescence was used an additional test of LPS activation of PMN. On addition of LPS (10 mug/ml) , slow but progressive light emission was noted. Normal peaking time ranged from 30 to 60 minutes with different intensities from different donors. Addition of platelet activating factor (PAF) as a primer did not enhance the response but instead slightly depressed the activity. LPS on its own can also act as a priming agent
An Empirical Investigation of Use of Information Technology among Small and Medium Business Organizations: A Bruneian Scenario
No full textElevated neutrophil respiratory burst activity in essential hypertensive patients.
No full textNeutrophils play a significant role in maintaining the integrity of innate immunity via their potent respiratory burst activity. However, the uncontrolled activation of respiratory burst in neutrophils also attributes to chronic diseases such as primary hypertension and atherosclerosis. In our study, we have investigated the activation of respiratory burst function of neutrophils harvested from essential hypertensive patients. In the presence of stimuli PMA and opsonized zymosan (OZ), hypertensive patients' neutrophils secrete significantly higher amount of superoxide anions compared to normotensive control. Although the magnitude of activation varies between both groups, yet the kinetics of activation is similar. When normotensive control's neutrophils were pre-treated with hypertensive serum, the cells failed to migrate toward fMLP which indicates the impairment of the migration property. In conclusion, the respiratory burst activity of neutrophils is affected by hypertension and their elevated superoxide anions production could be an aggravating factor in hypertension-related complicatio
Clinical-epidemiological pattern of primary immunodeficiencies in Malaysia 1987-2006: a 20 year experience in four Malaysian hospitals
No full textAim of study: To determine the clinical and epidemiological characteristics of patients seen with primary immunodeficiencies referred at four Malaysian Hospitals between 1987 to 2007 Methods: Patient data were retrospectively obtained from patient records and supplemented by information from a standardized questionnaires taken at the time of diagnosis from 4 participating hospitals. The completed data were transferred to document records kept by the first author. The diagnoses made were based on criteria set by WHO Scientific Committee 1986. Results: Fifty one (51) patients with completed records satisfied the criteria of primary immunodeficiencies based on WHO Scientific Committee 1986. Predominant Antibody deficiency (40.4%) is the commonest of the class of primary immunodeficiency (based on modified IUIS classification) followed by phagocytic defect (17.3%), combined immunodeficiencies (15.4%) and other cellular immunodeficiencies (11.5%). The commonest clinical presentation is pneumonia (54%). A positive Family history with a close family relative afflicted was a strong pointer to diagnosis for PID (52.6%) Primary immnodeficiencies are seen in all the major ethnic groups of Malaysia, predominantly among Malays. As observed in other patient registries, diagnostic delay remains the major cause of morbidity and mortality. Conclusion: Primary immunodeficiencies is relative rare but is an emerging disease in Malaysia. Creating awareness of the disease, may reveal more cases within the community. It is sufficient to be a health issue in Malaysia as in other developing countries in the future
Intellectual property laws and Islam in Malaysia.
No full textPhDThis study is undertaken on the premise that Islam and Islamic law is to be taken into
serious consideration in any future legislative reform of laws in Malaysia. Islam being
the religion of the country and the strong religious sentiment of the Muslims (who
form the majority in Malaysia) cannot be overlooked or dismissed lightly by the
legislators in Malaysia. Reformation of intellectual property laws is timely, as we are
now approaching to the dateline set by GATF-Trips agreement which aim is to
improve our standard of intellectual property protection. This study seeks to analyze
and evaluate the current legislation pertaining to intellectual property in Malaysia in
terms of the philosophy and rules governing the existence, ownership and exercise of
these rights and their consistency and inconsistency with Islam and Islamic law. The
main objective of this study is to prove that a coherent and logical conceptual
framework of ownership of intellectual property can be derived from an Islamic
perspective which not only offers the basis of rights but also defines the scope of
these rights. From the point of ownership of rights, support can be obtained from the
normative framework of property rights within the traditional classification of 'mal'
(property) and 'haqq al-milkiyyah' (ownership rights) under Islamic law. From the
point of exercise of rights, the exact scope can be defined from the analysis of
fundamental concepts which have been developed by Muslim jurists. It has been
established that Islam and Islamic law offers a sound and systematic paradigm, which
in deeper analysis, can satisfy both our current obligations under international
treatises, as well as our responsibility to practise our religion to the fullest
Stylistics of “Tarikh i Balami”
No full textAbstractTarikh i Balami", written by abu Ali Mohammad Ibn Abdollah Balami, Minister of Samanis in the fourth century, is one of the oldest books in Islamic period that contains the first step of creation till Arab raid and the prophet's life and the kings. Amir Mansur ibn Noah Samani ordered Translation of the book âTarikh al-Omam va al-Mulukâ of Tabari to his minister , Balami. But on several occasions he summarized The original book in the translation and used the other sources and removed something from his translation.  Different versions of this book show that many differences between eleven versions used for comparison, none of them became similar to each other. Replacing the oldest words with new words and the Arabic word with Persian word in the same meaning is one of problems that copyists have caused for stylistics of this book.  Writing "Tarikh i Balami" is related to the first period of Persian prose in Iran. During this time that took Samanis and Tahiris period, the authors have written in a simple style. This style of writing, also called Khurasani style, because the authors have lived in Khorasan. The style is also called Balami, the author of the book, because he was one of the most prominent writers of this genre.  Results of comparison between this book and the other books of this period, such as mughaddamih Shahnameh abu Mansuri, translation of Tafsir i Tabari, Hudud al-alam min al-Mashriq ela al-Maqrib, Tafsir i Pak andâ¦. show that the most important stylistic features in its language level are significant in some areas. One of them is the author tried to use Persian words, but sometimes the shorter and more familiar Arabic words have been replaced. -       Some verbs used in specific ways, for example, the old prefixes âÙراâ, âÙرÙâ, âبازâ,⦠are used with verbs. -       Using infinitives in a specific method for example âÙداÙستÙد Ú©Ù ÚÙ Ø®ÙاÙد بÙدÙâ, -       Using intransitive verb in The transitive meaning like â Ø¢Ùگا٠ک٠بخت Ùصر Ø¢Ù Ùزگت ÙÛرا٠کرد٠بÙØ¯Ø ØªÙرÛت برگرÙت٠بÙد ٠سÙخت٠â,-       Creating a gap between the âÙÙâ and verb for negation the verb for example âاÙدر سÛاست Ù٠رÙا باشد Ú©Ù Ø´Ùا را زÙد٠ÙاÙÙâ,-       adding âبâ at the beginning of the verb to emphasize and deleting it from imperative verbs, -       Using âبÙد٠بÙدâ as a verb, Using âاâ in verbs for praying or for changing the meaning like âاگر خبر Ø®Ûر است Ø®Øست٠ÙاÙÛا Ù Ùا٠خØست٠ÙاÙاد از ت٠در ÙرزÙدا٠آد٠تا ØÙا٠باشد. ٠اگر بداست Ø´Ù٠باشÛا Ù Ùا٠شÙÙ ÙاÙاد از ت٠تا ØÙا٠باشد.â⦠are some of the other stylistics Characteristics. Balami was very careful in translation to not affect his composition by the Arabic grammar. He has some innovations in translation too. Briefness, shortening sentences, using infinitives in a specific method, using abounded vocabularies, were seen in his Prose. Beauty metrics in writing have been different from those of now. For example, repeating verbs, nouns and prepositions at that time were popular and beautiful in prose but these techniques can be avoided these days. We may not be able to comment on the intellectual level by reading this book, because this book is a translated work of Mohammad ibn Jarir al-Tabari. For example, it can be spoken about sentences that he added to the original book after quoting histories. In this case it can be said he has been logical and wise man. There are some instances of this case. For example, he has written after the three narrations About the death of Moses: â these three narrations are superstitions and it is not appropriate to this book and those possess knowledge do not accept them.â But about the Iranian pre-Islamic stories he has added to the original book like âBahram i Choobinâ story, it can be said that it was because of his sense of patriotism. Because he has been one of pure Iranian families, the Balamis, he has tried to revive the Persian language and national rites.References1.     Anonymous Aouthor (1939). Moâjm ol-Tavarikh va al-Qasas. Tehran: Kulali Khavar press.2.     Arabi, MuhammadAli (1994). Translation Glossary Tabari commentary with The equivalent of Quran for Some words, Theses of MA, Mashad: Firdowsi University press.3.     Ashuri, Daryush (2001). Definitions and the concept of culture.Tehran: agah press.4.     Ayati, Abd al-Mohammad et al. (2007). Encyclopedia of Persian Language and Literature, Tehran: Academy of Persian Language and Literature.5.     Bahar, MuhammadTaqi (1991). Stylistics Or on the evolution of Persian prose. Tehran: Amir Kabir press.6.     Balami, Abu Ali Muhammad ibn Muhammad. (2006). Tarikh i Balami. Tehran: Zavvar press.7.     Chagani, Ibrahim (2003). Encyclopedic dictionary of language and languages. Khurram abad: Luristan University.8.     Dihkhuda, AliAkbar (2011). Persian dictionary. Tehran: Dihkhuda Persian dictionary Institude and Tehran University.9.     Farshidvard, Khosrow (1973). Decrease numerous Forms and shapes of Verb in Persian language, Guhar.No3.Pp305-313.10. Khanlari, Zahra (1969). The Dictionary of Dari Persian literature. Tehran: Now and Moein press.11. Kumiyli, Mukhtar (2011). An Introduction to stylistics works of Zoheiri Samarkandi, Fununi Adabi. No1. 3th year. Pp75-92.12. Miqdadi, Bahram (1999). Glossary of Terms for Literary Criticism. Tehran: Fikr i Ruz press.13. Moein, Muhammad (2007). Moein Persian dictionary. Tehran: Farhang i Mahrukh press.14. Muvaffaq Hiravi, abuMansur Ali (2010). al-Abniye an Haqaiq al-Adwiyyih. Tehran: Tehran University.15. Rizazadehmalik, Rahim (2003). Preface of Shahnameh Abu Mansuri and the introduction of Shahnamih. Tehran: Golab press.16. Safa, Zabihullah (2007). Literary History of Iran. Tehran: Quqnus press.17. Shamisa, Sirus (2007). Stylistics. Tehran: Payam i Nur University.Sharifi, Muhammad (2008). Dictionary of Persian Literature . Tehran: Now and Moein presses
Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021
No full textBackground: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk-outcome pairs. Pairs were included on the basis of data-driven determination of a risk-outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk-outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk-outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7-9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4-9·2]), smoking (5·7% [4·7-6·8]), low birthweight and short gestation (5·6% [4·8-6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8-6·0]). For younger demographics (ie, those aged 0-4 years and 5-14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9-27·7]) and environmental and occupational risks (decrease of 22·0% [15·5-28·8]), coupled with a 49·4% (42·3-56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9-21·7] for high BMI and 7·9% [3·3-12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6-1·9) for high BMI and 1·3% (1·1-1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4-78·8) for child growth failure and 66·3% (60·2-72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions. Funding: Bill & Melinda Gates Foundation
Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis
No full textUsing large-scale whole-genome sequencing, Dewan et al. identify pathogenic HTT repeat expansions in patients diagnosed with FTD/ALS neurodegenerative disorders. Autopsies confirm the TDP-43 pathology expected in FTD/ALS and show polyglutamine inclusions within the frontal cortices but no striatal degeneration. These data broaden the phenotype resulting from HTT repeat expansions
