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Fulltext Somatic mitochondrial DNA D-loop mutations in meningioma discovered: A preliminary data

Mohamed Yusoff AA, Mohd Khair SZN, Wan Abdullah WS, Abd Radzak SM, Abdullah JM

J Cancer Res Ther, 2020 12 22;16(6):1517-1521.
PMID: 33342822 DOI: 10.4103/jcrt.JCRT_1132_16

Background and Objective: Meningiomas are among the most common intracranial tumors of the central nervous system. It is widely accepted that the initiation and progression of meningiomas involve the accumulation of nucleus genetic alterations, but little is known about the implication of mitochondrial genomic alterations during development of these tumors. The human mitochondrial DNA (mtDNA) contains a short hypervariable, noncoding displacement loop control region known as the D-Loop. Alterations in the mtDNA D-loop have been reported to occur in most types of human cancers. The purpose of this study was to assess the mtDNA D-loop mutations in Malaysian meningioma patients.
Materials and Methods: Genomic DNA was extracted from 21 fresh-frozen tumor tissues and blood samples of the same meningioma patients. The entire mtDNA D-loop region (positions 16024-576) was polymerase chain reaction amplified using designed primers, and then amplification products were purified before the direct DNA sequencing proceeds.
Results: Overall, 10 (47.6%) patients were detected to harbor a total of 27 somatic mtDNA D-loop mutations. Most of these mtDNA mutations were identified in the hypervariable segment II (40.7%), with 33.3% being located mainly in the conserved sequence block II of the D310 sequence. Furthermore, 58 different germline variations were observed at 21 nucleotide positions.
Conclusion: Our results suggest that mtDNA alterations in the D-loop region may be an important and early event in developing meningioma. Further studies are needed, including validation in a larger patient cohort, to verify the clinicopathological outcomes of mtDNA mutation biomarkers in meningiomas.

Matched MeSH terms: Meningeal Neoplasms/blood; Meningioma/blood
Diagnostic and prognostic value of an immunofluorescent assay for melioidosis

Vadivelu J, Puthucheary SD

Am J Trop Med Hyg, 2000 Feb;62(2):297-300.
PMID: 10813488

Melioidosis caused by Burkholderia pseudomallei is endemic in southeast Asia. The clinical manifestations range from wound infections to acute septicemia. In some cases, recurrence can also occur following complete recovery. Case fatality rates are high and a major factor is the delay in the culture and identification of the bacterium. An immunofluorescent assay (IFAT) using whole-cell antigen for the detection of total antibodies to B. pseudomallei was tested with 650 sera. Using a cut-off value of 1:80, 66 sera from culture-confirmed cases were positive with titers > or = 320. In another 523 sera from patients in which no other etiology could be found, 149 (23.4%) were positive. To monitor disease activity, persistence of antibody levels was investigated on 61 serial sera samples collected from 14 other confirmed cases on follow-up visits while on oral maintenance therapy. The IFAT demonstrated a reduction in titers in cases of localized infections, suggesting that either the infection was being resolved or arrested while septicemic patients maintained high IFAT titers on follow-up, suggesting the possibility of continuous sequestration of antigen from an intracellular source.

Matched MeSH terms: Antibodies, Bacterial/blood*; Melioidosis/blood
Macular haemorrhage in adult acute leukaemia patients at presentation and the risk of subsequent intracranial haemorrhage

Jackson N, Reddy SC, Harun MH, Quah SH, Low HC

Br J Haematol, 1997 Jul;98(1):204-9.
PMID: 9233585

Retinal changes are common in adult acute leukaemia patients at presentation, but whether they correlate with the risk of subsequent intracranial haemorrhage is unknown. A 4-year study has been carried out in 82 newly-diagnosed acute leukaemia patients, aged 12-77 years, who were studied prospectively for the presence of intra-retinal haemorrhages (IRH), white-centred haemorrhages (WCH), cotton-wool spots (CWS) and macular haemorrhages (MH). Groups with and without these features were compared for their risk of intra-cranial haemorrhage (ICH) within the first 30 d following diagnosis. There was no association between the incidence of ICH and the presence of IRH, WCH or CWS. However, 6/13 of those with MH developed ICH, compared to 6/69 of those without MH (relative risk 5.0, CI 95% [2.03-12.33], P=0.003). The only other identifiable risk factor for ICH was the M3 subtype of AML, but if the four cases of M3-AML were discounted from analysis, MH remained a highly significant risk factor for ICH. Patients with MH should be monitored intensively for the development of ICH, and receive priority in the allocation of platelets where these are in short supply.

Matched MeSH terms: Blood Cell Count; Blood Coagulation Disorders/etiology
Fulltext Age-related reference intervals for free and total prostate-specific antigen in a Singaporean population

Saw S, Aw TC

Pathology, 2000 Nov;32(4):245-9.
PMID: 11186419

Cancer of the prostate is the sixth most frequently found cancer in Singapore. Prostate-specific antigen (PSA) is the most clinically useful tumour marker available today for the diagnosis and management of prostate cancer. To enhance the value of PSA as a screening test we developed age-specific intervals for our ethnic population. The measurement of free PSA was included in the study to calculate the free:total ratio which enhances the differential diagnosis of prostate cancer from benign prostatic hyperplasia or prostatitis. The total PSA upper limits of 10-year intervals, beginning at 30-years-old, were 1.4, 1.7, 2.3, 4.0, 6.3 and 6.6 microg/l. Free PSA cut-off limits were 0.4, 0.5, 0.5, 1.0, 1.5 and 1.6 microg/l. The free:total ratio of PSA was not age dependent. Abbott AxSym standardised their calibration material for both free and total PSA assays with the Stanford 90:10 reference material. This laboratory has implemented these age-specific reference intervals and are currently following up their pick-up rate in the detection of prostate cancer.

Matched MeSH terms: Prostatic Hyperplasia/blood*; Prostate-Specific Antigen/blood*
Fulltext Bone marrow and peripheral blood changes in non-Hodgkin's lymphoma

Lim EJ, Peh SC

Singapore Med J, 2000 Jun;41(6):279-85.
PMID: 11109344

47 patients with non-Hodgkin's lymphoma (NHL) were studied retrospectively to determine their marrow and blood changes at diagnosis.

Matched MeSH terms: Blood Cell Count; Lymphoma, Non-Hodgkin/blood*
Chemistry and biochemistry of palm oil

Sambanthamurthi R, Sundram K, Tan Y

Prog Lipid Res, 2000 Nov;39(6):507-58.
PMID: 11106812
Matched MeSH terms: Lipids/blood; Lipoproteins/blood
Application of the Serodia-HCV particle agglutination for the detection of antibodies to hepatitis C virus

Ooi BG, Sinniah M, Ismail S, Baharuddin R

Malays J Pathol, 1996 Dec;18(2):89-93.
PMID: 10879228

The Serodia-HCV Particle Agglutination (HCV-PA) for the detection of HCV antibodies was compared with the Enzyme Immunoassay Test (UBI HCV EIA) for possible in-house use. A total of 150 specimens were analysed using UBI HCV EIA and Serodia-HCV PA. Of these, 80 (53.3%) were both PA and EIA positive and 59 (39.3%) were negative by both techniques. Eleven sera (7.4%) were found to be EIA-positive but PA-negative. These 11 discordant sera were further tested by the LiaTek-HCV III Immunoassay (Organon Teknika). Ten were found to be line immunoassay negative and one was line immunoassay positive. Failure of the PA to detect the HCV positive serum meant that a small proportion of HCV antibody positives may be missed by the PA test. We conclude that (i) EIA should continue to be the first line screening test in our laboratory, (ii) PA with its 100% specificity could be a useful supplementary screen for all EIA-positive sera and finally (iii) line immunoassay could be used on sera to resolve discordant results in the EIA and PA assays.

Matched MeSH terms: Hepatitis C/blood; Hepatitis C Antibodies/blood*
Therapeutic equivalence of a low dose artemisinin formulation in falciparum malaria patients

Wong JW, Yuen KH, Nagappan S, Shahul WS, Ho SS, Gan EK, et al.

J Pharm Pharmacol, 2003 Feb;55(2):193-8.
PMID: 12631411

We have evaluated the therapeutic equivalence of a beta-cyclodextrin-artemisinin complex at an artemisinin dose of 150 mg, with a commercial reference preparation, Artemisinin 250 at a recommended dose of 250 mg. One hundred uncomplicated falciparum malarial patients were randomly assigned to orally receive either beta-cyclodextrin-artemisinin complex (containing 150 mg artemisinin) twice daily for five days or the active comparator (containing 250 mg artemisinin) twice daily for five days. The patients were hospitalized for seven days and were required to attend follow up assessments on days 14, 21, 28 and 35. All patients in both treatment groups were cured of the infection and achieved therapeutic success. At day seven of treatment, all patient blood was clear of the parasites and the sublingual temperature of all patients was less than 37.5 degrees C. Moreover, the parasite clearance time in both treatment groups was similar, being approximately three days after initiation of treatment. Comparable plasma artemisinin concentrations were observed between patients in both treatment groups at 1.5 and 3.0 h, although slightly higher levels were obtained with patients in the beta-cyclodextrin-artemisinin complex-treated group. The beta-cyclodextrin-artemisinin complex at a dose of 150 mg artemisinin was therapeutically equivalent to 250 mg Artemisinin 250. Additionally, patients receiving beta-cyclodextrin-artemisinin complex showed less variability in their plasma artemisinin concentrations at 1.5 h post-dosing, which suggested a more consistent rate of drug absorption.

Matched MeSH terms: Sesquiterpenes/blood; Artemisinins/blood
Comparative bioavailability study of two controlled-release pentoxifylline tablet preparations

Yuen KH, Wong JW, Peh KK, Julianto T, Choy WP

Drug Dev Ind Pharm, 2000 Jul;26(7):803-7.
PMID: 10872103

The bioavailability of a generic preparation of pentoxifylline sustained-release (SR) tablet was evaluated in comparison with a proprietary product (Trental 400). For the study, 12 healthy male volunteers participated; the study was conducted according to a randomized, two-way crossover design. The bioavailability was compared using the parameters total area under the plasma level-time curve AUC0-infinity, peak plasma concentration Cmax, and time to reach peak plasma concentration Tmax. No statistically significant difference was observed between the values of the two products in all three parameters. The 90% confidence interval for the ratio of the logarithmic transformed AUC0-infinity values of the generic pentoxifylline over those of Trental 400 was found to lie between 0.83 and 1.00, while that of the parameter Cmax was between 0.91 and 1.29. In addition, elimination half-life t1/2 and apparent volume of distribution Vd were calculated. There was no statistically significant difference between the t1/2 Vd values obtained from the data of the two preparations.

Matched MeSH terms: Hematologic Agents/blood; Pentoxifylline/blood
Fulltext An enzyme immunoassay for advanced glycosylation end-products in serum

Wan Nazaimoon WM, Khaid BAK

Malays J Pathol, 1998 Dec;20(2):83-9.
PMID: 10879267

We successfully developed an in-house, competitive enzyme immunoassay to measure advanced glycosylation end-products (AGE) in serum. The assay involved coating microtitre wells with AGE-BSA at 8 micrograms/ml for 4 hours, followed by overnight incubation of 20 microliters sample (prediluted at 1:6) with 80 microliters antiserum (1:8000). HRP-labelled goat anti-rabbit was used as the second antibody and 3,5',5,5'-tetramethylbenzidine dihydrochloride as the substrate. Incubation was carried out at 4 degrees C. As suggested in an earlier study, we standardised the AGE units against normal human serum (NHS). Thus, one AGE unit was defined as the inhibition that resulted when the 1:6 diluted NHS was assayed. Mean (+/- SD) AGE level in normal subjects (n = 37) was significantly lower than in diabetes subjects with microalbuminuria (n = 57) (6.0 +/- 0.7 versus 10.2 +/- 4.7 units/ml, p = 0.0001). With the availability of in-house assay and by standardising the AGE unit with the other laboratories, more studies could be undertaken and results compared, and possibly, further elucidate the roles of AGE in the pathogenesis of diabetic complications.

Matched MeSH terms: Diabetes Mellitus, Type 1/blood; Glycosylation End Products, Advanced/blood*
Gamma-scintigraphic study of the gastrointestinal transit and in vivo dissolution of a controlled release diclofenac sodium formulation in xanthan gum matrices

Billa N, Yuen KH, Khader MA, Omar A

Int J Pharm, 2000 May 15;201(1):109-20.
PMID: 10867269

A xanthan gum matrix controlled release tablet formulation containing diclofenac sodium was evaluated in vitro and was found to release the drug at a uniform rate. The gastrointestinal transit behaviour of the formulation as determined by gamma scintigraphy, using healthy male volunteers under fasted and fed conditions, indicated that gastric emptying was delayed with food intake. In contrast, the small intestinal transit remained practically unchanged under both food statuses. Therefore, the delay in caecal arrival observed in the fed state can be attributed to the delay in gastric emptying. Rate of diclofenac sodium absorption was generally higher in the fed state compared to the fasted state, however the total amount absorbed under both food statuses remained practically the same. The rate of in vivo dissolution of the drug in the fed state was faster compared to that in the fasted state. Thus, at the time of caecal arrival, in vivo dissolution was complete in the fed state, unlike in the fasted state, where almost 60% of the drug was delivered to the colon.

Matched MeSH terms: Anti-Inflammatory Agents, Non-Steroidal/blood; Diclofenac/blood
Quantification of (+)-calanolide A, a novel and naturally occurring anti-HIV agent, by high-performance liquid chromatography in plasma from rat, dog and human

Xu ZQ, Norris KJ, Weinberg DS, Kardatzke J, Wertz P, Frank P, et al.

J Chromatogr B Biomed Sci Appl, 2000 Jun 09;742(2):267-75.
PMID: 10901131

A HPLC method was validated for quantification of (+)-calanolide A (1), a novel anti-HIV agent, in rat, dog and human plasma. The synthetic intermediate (+/-)-12-oxocalanolide A (2) was found to be a suitable internal standard. Compounds were extracted from plasma using a solid-phase C(18) cartridge and quantified over the assay range of 12.5 to 800 ng/ml. The method was utilized to determine (+)-calanolide A pharmacokinetics in rats, dogs and humans. This is the first report of a validated HPLC assay for determination of (+)-calanolide A concentrations in rat and dog plasma as well as human plasma obtained from clinical trials. There was no evidence of in vivo epimerization of (+)-calanolide A to its inactive epimer (+)-calanolide B (3).

Matched MeSH terms: Coumarins/blood*; Anti-HIV Agents/blood*
Levels of serum IgG against Porphyromonas gingivalis in patients with rapidly progressive periodontitis, rheumatoid arthritis and adult periodontitis

Yusof Z, Porter SR, Greenman J, Scully C

J Nihon Univ Sch Dent, 1995 Dec;37(4):197-200.
PMID: 8820338

Levels of serum IgG against Porphyromonas gingivalis cell sonicate were determined in patients with rheumatoid arthritis (RA) (n = 25), rapidly progressive periodontitis (RPP)(n = 25) and adult periodontitis (AP)(n = 15) and controls (HP)(n = 10) utilizing the ELISA technique. Comparison between groups showed no significant differences between the HP and RA groups and also between the RPP and AP groups. The increased levels of IgG in the RPP and AP groups were comparable. Significant differences in IgG levels were noted between HP and RPP (p<0.05) and between HP and AP (p<0.01). The differences between RA and RPP and between RA and AP were highly significant (p<0.0001). Thus it was revealed that the serum levels of IgG against P. gingivalis in RPP and AP patients were elevated, whereas the levels in RA patients were comparable to those in controls.

Matched MeSH terms: Antibodies, Bacterial/blood*; Immunoglobulin G/blood*
Antigenic types of Orientia tsutsugamushi in Malaysia

Tay ST, Rohani MY, Ho TM, Devi S

Southeast Asian J Trop Med Public Health, 2002 Sep;33(3):557-64.
PMID: 12693591

The seroprevalence of various Orientia tsutsugamushi (OT) strains among Malaysian patients with suspected scrub typhus infections was determined using an indirect immunoperoxidase (IIP) assay. IgG against a single OT strain were detected in six sera (3 Karp, 1 Gilliam and 2 TC586), whereas IgM antibodies against a single OT strain (Gilliam) were noted in 3 sera (Gilliam). IgG reactive to all OT strains were present in 33 (47.1%) of the 70 sera and IgM reactive to all OT strains were present in 22 (78.6%) of the 28 sera. The fact that most sera were reactive to multiple OT strains suggests that group-specific antigens are involved in scrub typhus infections, whereas very few were due to strain-specific epitopes present on these strains. Peak IgG and IgM titers were noted more frequently against Gilliam, Karp, and TA763 strains: this suggests that these strains may be the commonest infecting strains among Malaysian patients. Two predominant OT polypeptides consistently reacted with patients' sera were the 70 kDa and 56 kDa proteins.

Matched MeSH terms: Immunoglobulin G/blood; Immunoglobulin M/blood
Treatment of chronic urticaria with thyroxine in an euthyroid patient with thyroglobulin and microsomal antibodies

Koh CK, Hew FL, Chiu CL

Ann Acad Med Singap, 2000 Jul;29(4):528-30.
PMID: 11056786

INTRODUCTION: The association of chronic urticaria and thyroid autoimmunity is not well recognised and the potential use of thyroxine in the treatment of chronic urticaria in patients with thyroid autoimmunity is even less well known.
CLINICAL PICTURE: We report a case of chronic urticaria in an euthyroid patient with evidence of significantly elevated levels of thyroglobulin and microsomal antibodies.
TREATMENT AND OUTCOME: Treatment with thyroxine has brought about clinical remission of the chronic urticaria but no change in the thyroid antibody levels could be demonstrated.
CONCLUSION: Patients with chronic urticaria should be screened for evidence of thyroid autoimmunity. A closely monitored trial of thyroxine therapy for those who have thyroid autoimmunity can be rewarding.

Matched MeSH terms: Autoantibodies/blood*; Thyroiditis, Autoimmune/blood
Effects of copper overload on hepatic lipid peroxidation and antioxidant defense in rats

Zhang SS, Noordin MM, Rahman SO, Haron J

Vet Hum Toxicol, 2000 Oct;42(5):261-4.
PMID: 11003114

The influence of copper (Cu) overload on hepatic lipid peroxidation and antioxidation defense capacity was studied by overloading rats with copper sulphate orally (500 mg Cu/kg bw) 5 d/w for 8 w. Malondialdehyde (MDA), Cu-Zn superoxide dismutase (SOD), and Se-glutathione peroxidase (GSH-Px) were measured in serum and liver homogenate at 2, 4 and 8 w of dosing. Liver Cu concentration and alanine aminotransferase (ALT) activity were also determined. As Cu loading progressed, there were multiparameter changes with significant ALT elevation, increased MDA concentrations in serum and liver homogenate, and dramatic declines of SOD and GSH-Px activities in erythrocytes and whole blood respectively, along with marked elevation of hepatic Cu in the Cu-dosed group. Excessive Cu accumulation in the liver depressed SOD and GSH-Px activities and resulted in high MDA in serum and liver homogenate due to the lipid peroxidation induced by the Cu overload.

Matched MeSH terms: Alanine Transaminase/blood; Malondialdehyde/blood
Effect of ovariectomy and sex hormones replacement on tumour marker enzymes under administration of chemical carcinogens in the rat

Zarida H, Wan Zurinah WN, Zanariah J, Michael LK, Khalid BA

Exp. Toxicol. Pathol., 1994 Mar;46(1):31-6.
PMID: 7916223

The effect of ovariectomy and sex hormone/s replacement in female rats was investigated by the determination of the tumour marker enzymes gamma-glutamyltranspeptidase (GGT) and alkaline phosphatase (ALP). This was compared to ovariectomized rats receiving sex hormone replacement and treated with carcinogen. Ovariectomy significantly increased the activity of plasma GGT. Plasma and microsomal ALP and microsomal GGT were unchanged. When replacements of estrogen (E), or progesterone (Prog), or combinations of both estrogen and progesterone were given to ovariectomized rats, the activity of plasma GGT was brought to the level of normal intact females. Treatment with carcinogen increased the PGGT activities in intact rats. In ovariectomized rats receiving carcinogen, the PGGT activities were significantly lower than in intact females and rats receiving both hormone replacement and carcinogen (p < 0.01). Carcinogen treatment in case of estrogen or progesterone replacement, either individually or in combination, showed GGT activities comparable to intact females receiving carcinogen. Both plasma and microsomal ALP were not affected by carcinogen administration. These results showed that ovariectomy reduced the severity of hepatocarcinogenesis while sex hormone replacement worsened the process.

Matched MeSH terms: Alkaline Phosphatase/blood; gamma-Glutamyltransferase/blood
Systemic Candida infection in University hospital 1997-1999: the distribution of Candida biotypes and antifungal susceptibility patterns

Ng KP, Saw TL, Na SL, Soo-Hoo TS

Mycopathologia, 2001;149(3):141-6.
PMID: 11307597

A total of 102 Candida species were isolated from blood cultures from January 1997 to October 1999. Using assimilation of carbohydrate test, 52 (51.0%) of the Candida sp. were identified as C. parapsilosis, 25.5% (26) were C. tropicalis. C. albicans made up 11.8% (12), 6.9% (7) were C. rugosa, 3.8% (4) C. glabrata and 1% (1) C. guilliermondii. No C. dubliniensis was found in the study. In vitro antifungal susceptibility tests showed that all Candida species were sensitive to nystatin, amphotericin B and ketoconazole. Although all isolates remained sensitive to fluconazole, intermediate susceptibility was found in 3 C. rugosa isolates. Antifungal agents with high frequency of resistance were econazole, clotrimazole, miconazole and 5-fluorocytosine. Candida species found to have resistance to these antifungal agents were non-C. albicans.

Matched MeSH terms: Candidiasis/blood; Cross Infection/blood
Fulltext Genetic causes of familial hypercholesterolaemia in a Malaysian population

Khoo KL, Van Acker P, Tan H, Deslypere JP

Med J Malaysia, 2000 Dec;55(4):409-18.
PMID: 11221151

A total of 86 unrelated Malaysian patients with familial hypercholesterolaemia (FH) were studied for mutations in their low-density lipoprotein receptor (LDL-R) gene. Amongst them, 23 had a LDL-R gene mutation, while none having an Apolipoprotein B-3500 (Apo B-3500) mutation. Patients with the LDL-R gene defect appeared to have a higher level of low-density lipoprotein cholesterol (LDL-C), an increased incidence of xanthomas and coronary heart disease (CHD), but no relationships were found between the type of LDL-R gene mutations and their lipid levels or clinical signs of CHD. In contrast to Western data, our findings seemed to indicate a predominance of mutations in the ligand binding domain and an absence of Apo B-3500 gene mutation. The latter finding may offer a genetic basis as to why Asian patients with familial hypercholesterolaemia have lower LDL-C levels and less premature CHD than their Western counterparts.

Matched MeSH terms: Hyperlipoproteinemia Type II/blood; Cholesterol, LDL/blood
Fulltext Detection of circulating antigens of Parastrongylus cantonensis in human sera by dot-blot ELISA and sandwich ELISA using monoclonal antibody

Eamsobhana P, Yong HS, Mak JW, Wattanakulpanich D

Southeast Asian J Trop Med Public Health, 1997 Sep;28(3):624-8.
PMID: 9561620

A dot-blot ELISA was compared with a previously performed sandwich ELISA for the detection of Parastrongylus cantonensis antigens in sera from patients. Using the same monoclonal antibody and the same sera, 6 of 10 sera (60%) from parastronglyiasis patients were positive in dot-blot ELISA, whereas with sandwich ELISA, 5 of the same patient sera (50%) were positive. The specificity in both assays was 100% using 50 sera from patients with other parasitic diseases; of these, 10 each were from patients with cysticercosis, filariasis, gnathostomiasis, malaria and toxocariasis. The control group consisted of 53 sera from normal health Thais and Malaysians. The sensitivity of the assays was, however, slightly better with dot-blot ELISA and because it is simple, quick and cost-effective, it may be a test of choice for specific diagnosis of human parastrongyliasis.

Matched MeSH terms: Antigens, Helminth/blood*; Strongylida Infections/blood

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