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Biomedical subjects

T Pang

Publications and source records attributed to T Pang.

At least 19 recordsLinked to original sources
PubMed2007

Minimally invasive parathyroidectomy using the lateral focused mini-incision technique without intraoperative parathyroid hormone monitoring.

BACKGROUND: Minimally invasive parathyroidectomy (MIP) involves scan-directed removal of a single adenoma through a 2.0-cm mini-incision without intraoperative monitoring. The aim of this study was to analyse the outcomes of MIP using such a simplified technique. METHODS: The study group comprised 500 consecutive patients undergoing MIP via a lateral mini-incision from August 2000 to September 2005. Levels of parathyroid hormone (PTH) were measured after operation solely to aid informed discharge. RESULTS: Some 97.4 per cent of patients were initially cured by MIP. Eight patients remained hypercalcaemic and a further five were normocalcaemic on the day after surgery but became hypercalcaemic again within 3 months of the procedure. Eleven of these patients were cured with subsequent re-exploration. Analysis of postoperative PTH data indicated that, at best, the use of intraoperative PTH measurement during surgery would have increased the cure rate by only a further 1 per cent. Three (0.6 per cent) of 500 patients had permanent recurrent laryngeal nerve palsy after MIP. CONCLUSION: MIP performed by the lateral focused mini-incision technique, without the use of intraoperative PTH monitoring, is a safe and effective procedure that results in outcomes equal to those of bilateral neck exploration.

Adenoma↗
PubMed2006

Introducing Vi polysaccharide typhoid fever vaccine to primary school children in North Jakarta, Indonesia, via an existent school-based vaccination platform.

OBJECTIVES: To report results on coverage, safety and logistics of a large-scale, school-based Vi polysaccharide immunization campaign in North Jakarta. METHODS: Of 443 primary schools in North Jakarta, Indonesia, 18 public schools were randomly selected for this study. Exclusion criteria were fever 37.5 degrees C or higher at the time of vaccination or a known history of hypersensitivity to any vaccine. Adverse events were monitored and recorded for 1 month after immunization. Because this was a pilot programme, resource use was tracked in detail. RESULTS: During the February 2004 vaccination campaign, 4828 students were immunized (91% of the target population); another 394 students (7%) were vaccinated during mop-up programmes. Informed consent was obtained for 98% of the target population. In all, 34 adverse events were reported, corresponding to seven events per 1000 doses injected; none was serious. The manufacturer recommended cold chain was maintained throughout the programme. CONCLUSIONS: This demonstration project in two sub-districts of North Jakarta shows that a large-scale, school-based typhoid fever Vi polysaccharide vaccination campaign is logistically feasible, safe and minimally disruptive to regular school activities, when used in the context of an existing successful immunization platform. The project had high parental acceptance. Nonetheless, policy-relevant questions still need to be answered before implementing a widespread Vi polysaccharide vaccine programme in Indonesia.

Antigens, Bacterial↗
PubMed2004

Role of tetrahydrobiopterin in adrenocorticotropic hormone-induced hypertension in the rat.

Adrenocorticotropic hormone (ACTH)-induced hypertension in the rat is characterized by nitric oxide deficiency. Tetrahydrobiopterin (BH4) is an essential cofactor for the enzyme nitric oxide synthase and glucocorticoids have been reported to reduce cytokine-induced BH4 production. Accordingly we hypothesized that ACTH-induced hypertension would be reversed by BH4 supplementation. Male Sprague-Dawley rats (n = 33) were treated with BH4 in vehicle (10 mg/kg/day i.p.) or vehicle alone (5 mg/kg/day i.p. of ascorbic acid in 4 mM HCl) for 10 days. ACTH (0.2 mg/kg s.c.) or saline daily injection was started 2 days after BH4 or vehicle treatment and continued for 8 days. Systolic blood pressure (SBP) was measured on alternate days using the tail cuff method. Treatment with HCl, ascorbic acid or BH4 alone had no effect on SBP. In saline treated rats, neither BH4 nor its vehicle modified SBP. In ACTH treated rats, SBP was increased in both BH4 (from 128 +/- 6 to 142 +/- 4 mmHg, T0 to T10, P < 0.0005, one way ANOVA) and vehicle groups (from 127 +/- 3 to 158 +/- 7 mmHg, T0 to T10, P < 0.001, one way ANOVA). There was no significant difference in SBP between BH4 + ACTH treated and vehicle + ACTH treated rats. Thus, daily injection of BH4 (10 mg/kg i.p.) failed to prevent the development of ACTH-induced hypertension in rat.

Adrenocorticotropic Hormone↗
PubMed2003

Synthesis and secretion of molecules exhibiting the HL1 epitope during development of the hyaline layer of the asteroid Pisaster ochraceus.

A complex ECM layer called the hyaline layer (HL) surrounds embryos and larvae of the starfish Pisaster ochraceus. When preserved by freeze substitution, the HL of a bipinnaria larva consists of six sublayers. From the plasmalemma outwards these are the intervillous layer (iv), the H3, H2, H1 sublayers that make up the supporting layer, a boundary layer (b) and the coarse outer meshwork (cm). HL development begins at fertilization when exocytosis of the cortical granules releases ECM into the perivitelline space and elevates the fertilization membrane. Over the course of early development the layers are added in a sequential manner and by hatching the embryo is surrounded by a thin HL containing most if not all of the layers. The layers thicken over the next few days. By the bipinnaria stage the larvae are surrounded by a thick six-layered HL. HL1 is a monoclonal antibody that reacts against an epitope found in all regions of the HL of the bipinnaria larva except the H2 sublayer. Western blots show that it is present on several molecules during HL development. The number and pattern of the HL1-labeled molecules change during development, suggesting that either new molecules are being produced or that some molecules are precursors of others. Light (immunofluorescence) and TEM (immunogold) studies using HL1 in the early stages of development show that HL1-positive material is not present in the corticle granules and that it only begins to be manufactured and secreted in quantity in the blastula stage at 18-20 h. Following this it continues to be secreted at least as far as the bipinnaria stage. Molecules containing the HL1 antigen therefore do not appear to play a major role in early development of the HL but are necessary for later events. The results suggest that, like the sea urchin HL, the starfish HL undergoes a sequential organization of the different HL layers from ECM components, which are released into the perivitelline space.

Animals↗
PubMed2003

Ethnic distribution of Chlamydophila pneumoniae antibodies in a Malaysian population and possible correlation with coronary heart disease.

Chlamydophila pneumoniae, an important respiratory pathogen causing lower respiratory tract infections, has also been implicated in coronary heart disease (CHD). This study reports a cross-sectional, demographic, serological analysis of the prevalence of Chlamydophila pneumoniae antibodies in a multiracial Malaysian population. Generally, Malaysian Indians had the highest degree of seropositivity (58%) followed by the Chinese (54%) and the Malays (32%), results which were statistically significant (CI: 95%; p < 0.01). Interestingly, this trend was also reflected in the study group consisting of patients with acute myocardial infarctions (AMI) and chronic CHD. Again, the Indians were more frequently seropositive (65%), with more than 50% having IgG titres > or = 128. Comparatively, the Chinese and Malays showed 51 and 17% seropositivity respectively. These results were also statistically significant (CI: 95%; p < 0.01). Malaysian Indians are more commonly afflicted with CHD. A variety of factors have been suggested to explain this prevalence including diet, social habits, genetics and the possible role of infectious agents. This study notes an interesting association between this pattern of racial prevalence and the possible role of C. pneumoniae infections as a contributory/predisposing factor in the development of cardiovascular disease.

Adult↗
PubMed2002

Ultrastructural aspects of the development of the hyaline layer and extracellular matrix lining the gastrointestinal tract in embryos and larvae of the starfish Pisaster ochraceus preserved by freeze substitution.

Embryos and larvae of the starfish Pisaster ochraceus are surrounded by a complex extracellular matrix (ECM) layer called the hyaline layer (HL). A similar but less well-organized ECM layer lines some regions of the larval gut. Examination of material preserved by freeze substitution shows that the HL consists of a coarse outer meshwork, a boundary layer, a supporting layer, which is divided into three sublayers, H1, H2, and H3, and an intervillus layer. The development of the HL has been studied in material preserved by freeze substitution. Development begins at fertilization when exocytosis of the cortical granules releases ECM into the perivitelline space and elevates the fertilization membrane. Shortly after, plaques of dense material with attached fibers are present on the outer surface of the egg plasmalemma. Following this, these plaques and fibers are associated with the tips of short microvilli, suggesting that they may induce microvillus formation. Next, the tips of some of the microvilli are joined by short regions of the H1 sublayer. Some of these H1 regions have short segments of boundary layer material associated with their outer surfaces while others are naked. Just prior to hatching, the H1 and boundary layers completely surround the embryo, separating the developing coarse meshwork and intervillus layers. Short segments of the H2 and H3 sublayers are also present. Posthatching, the microvilli and all HL layers increase in thickness and density, particularly the H2, boundary, and coarse outer meshwork layers. The results suggest a sequential organization of HL components from ECM that is secreted into the perivitelline space.

Animals↗
PubMed2001

Comparison of safety and immunogenicity of a Vi polysaccharide typhoid vaccine with a whole-cell killed vaccine in Malaysian Air Force recruits.

OBJECTIVE: To carry out a comparative study of the safety and immunogenicity of Vi polysaccharide vaccine against whole-cell killed (WCK) typhoid vaccine. METHODS: The study was carried out on young adult recruits (aged 18-25 years) of the Malaysian Air Force. A total of 125 subjects received the Vi polysaccharide vaccine and 114 received the WCK vaccine. FINDINGS: The Vi vaccine was significantly less reactogenic than the WCK vaccine with regard to systemic and local reactions. Following administration of the Vi vaccine, seroconversion rates (defined as the percentage of subjects with a 4-fold rise of baseline antibody level) of 75.5% and 67% were observed at 2 weeks and 6 weeks, respectively, after immunization, compared with 25% and 31.3% among recipients of the WCK vaccine. Of the 110 Vi vaccinees with serological data, 21 (19%) had high, seroprotective, pre-immunization levels of anti-Vi antibodies (> or = 1 microgram/ml). The majority of subjects in this group came from a region in Malaysia which is known to have high typhoid endemicity. Interestingly, these antibody levels were boosted considerably following administration of vaccine at a level that was 5-fold higher than in subjects with low pre-immunization levels. In contrast, the seroconversion rates in those receiving the Vi vaccine were higher in subjects with low pre-immunization levels of anti-Vi antibodies (76-84%), compared to those with protective levels of > or = 1 microgram/ml prior to immunization (48-57%). CONCLUSIONS: The study reaffirms the safety and efficacy of the Vi polysaccharide vaccine and identifies a hitherto unrecognized advantage in its use, i.e. it is a potent immunogen that boosted considerably the protective antibody levels among a significant number of immunologically sensitized individuals living in typhoid-endemic regions.

Adolescent↗
PubMed2001

HPV16 E6 gene variations in invasive cervical squamous cell carcinoma and cancer in situ from Russian patients.

HPV16 is frequently seen in invasive cervical cancer (ICC) and cervical intraepithelial neoplasia (CIN). Its E6 gene has frequent sequence variations. Although some E6 variants have been reported to have different biochemical or biological properties, they do not show geographical identity. Moreover, the definition of 'variant' has been a source of confusion because it has been based on all departures from the 'prototype' once isolated randomly from an ICC case. We amplified the HPV16 E6 gene by PCR from fresh-frozen tissue of 104 cases of ICC and CIN from Russian patients and sequenced it in positive cases. We found that 32 of 55 (58.2%) ICC cases and 18 of 49 (36.7%) CIN cases were HPV 16-positive and we could identify 3 groups of E6 variants: group A was characterized by G at nt 350 where group B had T, and group M was a heterogeneous mixture of unique E6 variants; no significant difference existed in the distribution of the different groups between ICC and CIN; the clinically malignant (as defined by FIGO stage) order between the groups was M > A > B in ICC; in the cases with a single HPV16 E6 sequence, coexisting ICC, CIN and normal epithelium in the same patient shared the E6 variant; and 4 cases of ICC had double/multiple E6 variants. The results did not show any importance of E6 variants for ICC progression in Russian women. The results also indicated that the original HPV16 variant persisted during ICC progression, and that at a low frequency, double infections and/or mutation of variants might occur.

Adult↗
PubMed2001

Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers.

The Na+/H+ exchangers (NHEs) comprise a family of transporters that catalyze cell functions such as regulation of the pH and volume of a cell and epithelial absorption of Na+ and bicarbonate. Ubiquitous calcineurin B homologous protein (CHP or p22) is co-localized and co-immunoprecipitated with expressed NHE1, NHE2, or NHE3 independently of its myristoylation and Ca2+ binding, and its binding site was identified as the juxtamembrane region within the carboxyl-terminal cytoplasmic domain of exchangers. CHP binding-defective mutations of NHE1-3 or CHP depletion by injection of the competitive CHP-binding region of NHE1 into Xenopus oocytes resulted in a dramatic reduction (>90%) in the Na+/H+ exchange activity. The data suggest that CHP serves as an essential cofactor, which supports the physiological activity of NHE family members.

Amino Acid Sequence↗
PubMed2001

Oncogene lineages of human papillomavirus type 16 E6, E7 and E5 in preinvasive and invasive cervical squamous cell carcinoma.

Human papillomavirus (HPV)16 accounts for about 60% of the HPV infections in invasive cervical cancer (ICC). There are many sequence variations within HPV16, some of which have been associated with different biological properties, although no definite correlations have yet been established. However, the definition 'variant' has been a source of confusion in research and diagnosis, since it is based on all sequence deviations from a randomly selected prototype. This study has sequenced the HPV16 oncogenes E6, E7 and E5 from 61 Swedish cases with cervical intraepithelial neoplasia grade III (CIN III) or ICC. Clustering the sequence variations at the three common sites of variation (nucleotide 350 in E6, which has previously been associated with the progression from CIN III to ICC, and nucleotides 3979 and 4042 in E5) resulted in the distinction of three major oncogene lineages encompassing more than 95% of the cases, and two minor oncogene lineages. Simple comparison of the distribution of the individual variations or oncogene lineages between CIN III and ICC showed no significant difference, but the number of variations in addition to the three common ones was significantly higher in ICC. This novel classification scheme, based on the variations in the E6, E7 and E5 region, is considered to be a major improvement over the classical 'prototype-variant' classification, and can help to clarify the interpretation of HPV sequence data in relation to the progression of cervical cancer.

Carcinoma, Squamous Cell↗
PubMed2000

Second mutations rescue point mutant of the Na(+)/H(+) exchanger NHE1 showing defective surface expression.

We studied the effect of point mutation within the putative 11th transmembrane domain (TM11) of the Na(+)/H(+) exchanger NHE1 on the plasma membrane expression. Of the 19 mutants tested, two mutants (Tyr454 or Arg458 replaced by Cys) were retained in the endoplasmic reticulum. Interestingly, Y454C was expressed on the cell surface when one of the endogenous cysteine residues at position 8, 133, 421, or 477 was substituted with alanine. Random mutagenesis at Cys8 and its surrounding residues in the cytosolic N-tail revealed that replacement of Cys8 with Ala was the only identified single residue mutation that rescued Y454C. These results suggest that the abnormal conformation of the region of TM11 containing the Y454C mutation is compensated by the second mutation within other domains such as the N-tail. This approach may provide evidence for the interdomain interaction in NHE1.

Alanine↗
PubMed2000

A novel topology model of the human Na(+)/H(+) exchanger isoform 1.

The membrane topology of the human Na(+)/H(+) exchanger isoform 1 (NHE1) was assessed by substituted cysteine accessibility analysis. Eighty-three cysteine residues were individually introduced into a functional cysteineless NHE1, and these mutants were expressed in the exchanger-deficient PS120 cells. The topological disposition of introduced cysteines was determined by labeling with a biotinylated maleimide in the presence or absence of preincubation with the membrane-impermeable sulfhydryl reagent, 2-trimethylammoniumethyl-methanethiosulfonate in streptolysin O-permeabilized or nonpermeabilized cells. We proposed a new model for the topology of NHE1 that is significantly different from the model derived from hydropathy analysis. In this model, NHE1 is composed of 12 transmembrane segments (TMs) with the N and C termini located in the cytosol. The large, last extracellular loop in the membrane domain of the original model was suggested to comprise an intracellular loop, a new transmembrane segment (TM11), and an extracellular loop in the new model. Interestingly, cysteines at 183 and 184 and at 324 and 325 mapped to intracellular loops connecting TMs 4 and 5 (IL2) and TMs 8 and 9 (IL4), respectively, were accessible to sulfhydryl reagents from the outside. Furthermore, exchange activities of two mutants, R180C and Q181C, within IL2 were markedly inhibited by external MTSET. These data suggest that part of IL2 or IL4 may be located in a pore-lining region that is accessible from either side of the membrane and involved in ion transport.

Amino Acid Sequence↗
PubMed2000

Lithium activates mammalian Na+/H+ exchangers: isoform specificity and inhibition by genistein.

Replacement of external NaCl with LiCl induced cytoplasmic alkalinization in CCL-39 cells and rat L6 myoblasts expressing the endogenous Na+/H+ exchanger isoform NHE1. This Li+-induced alkalinization is due to activation of the Na+/H+ exchanger because it was completely inhibited by 100 microM ethylisopropylamiloride (apparent Kd=1 microM) and because it did not occur in exchanger-deficient PS120 cells. The effect of Li+ was not mimicked by Na+, K+, Cs+ and choline+. Li+ caused cytoplasmic alkalinization in PS120 cells expressing NHE1 or NHE2, but not NHE3, when Li+ was added to cells at a concentration high enough to saturate their external transport sites as predicted from Li+ affinities. Li+ did not induce phosphatidylinositol (PI) turnover or intracellular Ca2+ mobilization. Li+-induced alkalinization was not affected by protein kinase C down-regulation, loss of glycogen synthase kinase 3beta caused by antisense oligonucleotide treatment, or pretreatment with calphostin C, pertussis toxin, MEK inhibitor PD98059 and PI3-kinase inhibitor LY294002. However, it was markedly suppressed by the tyrosine kinase inhibitor genistein (10 microM). Thus, externally added Li+ activates NHE1 and NHE2 via a mechanism possibly involving a tyrosine kinase, causing an increase in cytoplasmic pH that could potentially affect various cell functions.

Alkalies↗
PubMed2000

Genotypic characterization of Salmonella typhi by amplified fragment length polymorphism fingerprinting provides increased discrimination as compared to pulsed-field gel electrophoresis and ribotyping.

Amplified fragment length polymorphism (AFLP) is a recently developed, PCR-based high resolution fingerprinting method that is able to generate complex banding patterns which can be used to delineate intraspecific genetic relationships among bacteria. In the present study, AFLP was evaluated for its usefulness in the molecular typing of Salmonella typhi in comparison to ribotyping and pulsed-field gel electrophoresis (PFGE). Six S. typhi isolates from diverse geographic areas (Malaysia, Indonesia, India, Chile, Papua New Guinea and Switzerland) gave unique, heterogeneous profiles when typed by AFLP, a result which was consistent with ribotyping and PFGE analysis. In a further study of selected S. typhi isolates from Papua New Guinea which caused fatal and non-fatal disease previously shown to be clonally related by PFGE, AFLP discriminated between these isolates but did not indicate a linkage between genotype with virulence. We conclude that AFLP (discriminatory index=0.88) has a higher discriminatory power for strain differentiation among S. typhi than ribotyping (DI=0.63) and PFGE (DI=0.74).

DNA Fingerprinting↗
PubMed2000

Multidrug-resistant strains of Salmonella enterica serotype typhi are genetically homogenous and coexist with antibiotic-sensitive strains as distinct, independent clones.

OBJECTIVE: The goal of this study was to report the molecular analysis of antibiotic-sensitive and multidrug-resistant (MDR) strains of Salmonella typhi, using pulsed-field gel electrophoresis (PFGE), with a particular emphasis on the coexistence of these strains in a typhoid-endemic region of Karachi, Pakistan. METHODS: One hundred isolates of S. typhi in humans (50 MDR and 50 antibiotic-sensitive isolates) from sporadic cases of typhoid fever were analyzed by Vi-phage typing, antibiograms and PFGE. RESULTS: The MDR S. typhi strains were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole. Analysis by PFGE showed that 50 MDR isolates of S. typhi had a single, homogenous PFGE profile, which was distinctly different from that of 50 antibiotic-sensitive isolates obtained in the same time frame from the same area. This latter group of isolates showed much greater diversity of PFGE profiles, as has been observed in other endemic regions. CONCLUSIONS: Multidrug-resistant and antibiotic-susceptible strains of S. typhi can coexist in endemic areas as epidemiologically independent pathogens and are not in competition for continued persistence and transmission.

Adolescent↗
PubMed2000

Localization and partial characterization of a molecule found in the plasma membrane of starfish and sea urchin embryos using a novel monoclonal antibody.

A monoclonal antibody, P212, has been developed which reacts against 120 kD and 90 kD proteins, P212 antigens found in the plasma membranes of both starfish and sea urchin embryos. Immunocytochemical studies with colloidal gold tagged P212 showed that the P212 antigens are also found on the inner membranes of several different types of granules and vesicles located in the eggs and cytoplasm of embryonic cells, and in the trans region of the Golgi apparatus. One or both of the P212 antigens are also found in the cortical granules, granules which are exocytosed at fertilization. They are not found on intracellular membrane structures such as the rough endoplasmic reticulum, the nuclear membrane, or a number of deeper granular structures. The P212 antigens are probably located on the membranes of vesicles which are on the exocytosis-endocytosis pathway and may be involved in cell trafficking.

Animals↗