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Biomedical subjects

I Chan

Publications and source records attributed to I Chan.

16 recordsLinked to original sources

Cutaneous Waldenström's macroglobulinaemia.

We report a case of Waldenström's macroglobulinaemia that presented with infiltrated skin nodules and plaques but without systemic symptoms. Cutaneous manifestations such as purpura, oedema, urticaria and ulceration may be seen in Waldenström's macroglobulinaemia and are a consequence of hyperviscosity, cryoglobulinaemia and/or tissue deposition of immunoglobulins. Direct cutaneous infiltration by neoplastic lymphoid cells is less common, and very rare as the initial presentation of Waldenström's macroglobulinaemia.

Aged↗

Molecular basis of lipoid proteinosis in a Libyan family.

Lipoid proteinosis is an autosomal recessive condition associated with variable scarring and infiltration of skin and mucosae. The disorder has recently been shown to result from loss-of-function mutations in the extracellular matrix protein 1 gene (ECM1) on 1q21. Extracellular matrix protein 1 has important physiological and biological roles in aspects of epidermal differentiation, binding of dermal collagens and proteoglycans, and in regulation of angiogenesis. Thus far pathogenic mutations have been described in 16 different families with lipoid proteinosis throughout the world. In this report, we describe the clinico-pathological features of a 10-year-old boy with lipoid proteinosis from a consanguineous Libyan family. By direct sequencing of the affected individual's genomic DNA, we identified a homozygous nonsense mutation in exon 2 of the ECM1 gene, Q32X. This mutation is the most 5' of all ECM1 mutations described thus far and is predicted to ablate the ECM1a, ECM1b and ECM1c splice variants of the ECM1 gene and to result in a severe clinical phenotype. Sequencing of DNA from the affected individual's five siblings revealed that four were heterozygous carriers of Q32X, findings that have important implications for genetic counselling given the high frequency of consanguineous marriages in Libya.

Child↗

Capsular intravascular endothelial hyperplasia: a peculiar form of vasoproliferative lesion associated with thyroid carcinoma.

AIMS: Florid vasoproliferative processes are uncommon in the thyroid gland. We report three cases of an unusual vasoproliferation involving the capsular blood vessels of thyroid carcinoma. METHODS AND RESULTS: The histological diagnoses of the three cases were made on conventional histological sections. Two cases were minimally invasive follicular carcinomas and one case was an encapsulated variant of papillary carcinoma. Some blood vessels in the tumour fibrous capsule were filled with spindly cellular proliferations forming irregular vascular clefts and papillae. Immunohistochemical studies for CD31, CD34 and muscle-specific actin confirmed that the spindly cells were mostly endothelial cells variably supported by pericytes. CONCLUSION: This peculiar intravascular endothelial hyperplasia by itself should not be mistaken for vascular invasion by tumour, but evidence of malignancy must be diligently sought by extensive sampling because the lesion has thus far been consistently associated with malignant thyroid neoplasms.

Actins↗

Synvisc perisynovitis.

Synvisc (hylan G-F 20) is a high molecular weight hyaluronan which is manufactured from chicken combs. It is currently one of the options used in the treatment of severe osteoarthritis of the knee joint. Synvisc is directly injected into the diseased joint, where it provides elasticity and viscosity. Published experience suggests than Synvisc is a safe and well-tolerated material with occasional mild local reactions but no long-term adverse sequelae. This article describes a case of Synvisc-related granulomatous inflammation in the perisynovial adipose tissue. To our knowledge, this is the first histological account of tissue reaction to Synvisc.

Adipose Tissue↗

Kappa-opioid receptor stimulation increases the expression of Na+-H+ exchange gene in the heart.

Kappa-opioid receptor (OR) stimulation increases intracellular pH (pHi) via activating the Na+-H+ exchange (NHE). In the present study, we determined the expression of the gene of NHE1, the predominant NHE isoform in the heart, and intracellular pH (pHi) upon kappa-OR stimulation in the rat heart. We found that 1 microM U50,488H (trans-3,4-dichloro-N-methyl-N-(2-(1 pyrrolidinyl)cyclohexyl)benzeneacetamide), a selective kappa-OR agonist, increased the expression of the NHE1 gene. We also found that U50,488H dose-dependently increased pHi in the heart. The effects were abolished by 1 microM nor-binaltorphimine (nor-BNI), a selective kappa-OR antagonist, indicating that the events were kappa-OR mediated. The effects on both NHE1 gene expression and pHi were also abolished by 5 microM chelerythrine and 5 microM BSM (bisyndolylmaleimide), protein kinase C (PKC) inhibitors, indicating that PKC mediated the actions. In addition, the effect of U50,488H on pHi was blocked by 10 microM EIPA (ethylisopropyl amiloride), a NHE1 inhibitor, indicating that NHE1 also mediated the action of U50,488H. The present study provides evidence for the first time that kappa-OR stimulation increased the NHE1 gene expression in the heart via a PKC dependent pathway. Kappa-OR stimulation also increases pHi via PKC and NHE in the heart.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

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Journal Article↗

Functional oral-motor skills: Do they change with age?

Dysphagia, a difficulty eating or drinking, appears to increase with age and is a concern for our growing elderly population. Mastication, tongue mobility, and lip closure are skills of the oral phase of ingestion, and have been shown to deteriorate with age. However, it is not clear whether these changes affect functional feeding. It is also unclear whether dysphagia is the result of the aging process itself, or whether it is secondary to disease. Therefore, the purpose of this study was to identify changes during the oral phase of ingestion in a group of healthy seniors. Functional feeding skills and oral praxis abilities were measured in 79 healthy adults aged 60-97 years. The Modified Functional Feeding Assessment (FFAm) subscale of the Multidisciplinary Feeding Profile (MFP) and the Oral Praxis Subtest (OPS) of the Southern California Sensory Integration Test were administered respectively. An interview followed to obtain information on denture wear, use of hearing aids and glasses, and types of foods avoided. Seniors maintained functional feeding skills throughout the four decades studied. These skills were not age-dependent, but depended on whether or not subjects wore full dentures. Even though all of the seniors maintained functional feeding skills, more seniors in the younger group (7th decade 60%, 8th decade 67%) had difficulty with a variety of food textures such as soft, hard, fibrous, and some with tough skins, than the older group (9th decade 40%, 10th decade 44%). Oral praxis abilities were correlated significantly with age, but not with hearing aid use. Overall, healthy seniors maintained their functional feeding and oral praxis skills. Good health and natural dentition appear to be excellent indicators for functional feeding ability.

Aged↗

A two-dose hepatitis B vaccine regimen: proof of priming and memory responses in young adults.

This study shows that two doses of a recombinant hepatitis B vaccine (10 micrograms or 20 micrograms of HBsAg per dose), administered 6 months apart to young, healthy adults, can induce an antibody (anti-HBs) response similar to that expected with the standard three-dose regimen of this vaccine given at intervals of 0, 1, and 6 months. While only 46-67% of the vaccinees displayed a protective anti-HBs titer of > or = 10 mIU ml-1 prior to the receipt of the second dose at 6 months, virtually all were primed as 97-99% of the subjects developed such a titer when tested a month after the second dose. Among vaccinees given 10 or 20 microgram doses, respectively, the secondary rise in antibody following the second dose yielded geometric mean titers (GMTs) of 1103 and 2538 mIU ml-1, respectively. The study further demonstrated that a two-dose regimen of vaccination induced strong immunologic memory for HBsAg, as a booster dose of vaccine given 2 years later resulted in a rapid and vigorous anamnestic antibody response.

Adolescent↗

Five paediatric case reports of the use of adenosine in supraventricular tachycardia.

The efficacy, safety and diagnostic usefulness of adenosine in the treatment of supraventricular tachycardia in children were prospectively studied over a 2-year period. Only patients who were stable and without hypotension were included. Adenosine was given at a dose of 0.1 mg/kg and increased to 0.2 mg/kg for the second and third doses if there was no response. Adenosine was used on 5 occasions in 5 patients. Adenosine was found to be effective in terminating supraventricular tachycardia in all 5 patients; 4 responded to a dose of 0.2 mg/kg while 1 responded to 0.1 mg/kg. Wolff-Parkinson White Syndrome was detected in 2 patients after termination of supraventricular tachycardia. Transient hypotension was noted in 1 patient lasting 45 seconds with no haemodynamic consequences. Two patients had transient ventricular ectopics lasting 3 to 5 seconds. One out of 3 patients who were old enough to report side-effects, experienced chest discomfort and dizziness lasting 5 seconds. All side-effects were transient and mild. We concluded that adenosine is effective and safe in terminating supraventricular tachycardia in children after vagal manoeuvres have failed.

Adenosine↗

Prevalence of Dientamoeba fragilis antibodies in children and recognition of a 39 kDa immunodominant protein antigen of the organism.

Dientamoeba fragilis, a common intestinal protozoan parasite in Canada, has been associated with diarrhoea and abdominal pain in some patients. Seroprevalence of this organism has not been reported previously. In the present study sera from three symptomatic patients, 12 age- and sex-matched controls, and 189 randomly selected healthy individuals (age 6 months to 19 years) were tested for antibodies against Dientamoeba fragilis by an indirect immunofluorescence (IIF) assay. All three symptomatic patients infected with Dientamoeba fragilis had positive IIF titres of 80, and all 12 matched controls had positive titres ranging 20 to 160 (geometric mean titre 48). Of the 189 healthy children, 172 (91%) were positive at a serum dilution of 1:10 or higher. The specificity of the IIF assay was reinforced by immunoblotting 20 representative serum samples against Dientamoeba fragilis. In all 17 IIF-positive serum samples, a 39 kDa protein band of Dientamoeba fragilis was identified, the same band recognized by a mouse monoclonal antibody raised in our laboratory. Findings over a five-year period indicate that Dientamoeba fra-gilis was the most common protozoan, followed closely by Giardia lamblia and more distantly by Cryptosporidium parvum. The high seropositivity of 91% for Dientamoeba fragilis compares reasonably well with serologic data obtained by IIF and reported previously for Giardia lamblia (85.6%) and Cryptosporidium parvum (86%).

Adolescent↗

An amino-terminal fragment of human lipopolysaccharide-binding protein retains lipid A binding but not CD14-stimulatory activity.

LPS-binding protein (LBP) mediates the pro-inflammatory effects of bacterial LPS by enhancing LPS-induced cytokine production by monocytic cells. LBP binds specifically to LPS to generate a complex that interacts with the CD14 receptor on the surface of responsive cells. To identify the biologically active regions of the protein responsible for mediating these activities, we cloned and expressed human rLBP (456 amino acids) as well as a truncated form encoding amino acids 1-197 (rLBP25). Both forms of LBP bound to LPS with the same affinity, and similarly inhibited LPS activity in the Limulus amebocyte lysate assay. These results demonstrate that the LPS-binding domain of LBP resides entirely within the N-terminal 197 amino acids of the protein. rLBP and rLBP25 were compared for their ability to mediate CD14-dependent LPS effects on cells. rLBP was effective in mediating uptake of LPS and stimulation of TNF production by human monocytic THP-1 cells, whereas rLBP25 had no significant activity in these assays. Similarly, rLBP was able to mediate LPS-induced TNF production by human PBMC whereas rLBP25 was essentially inactive. These results suggest that the structural features of LBP required for mediating LPS effects via CD14 are probably located in the C-terminal region of the protein. Thus, the LPS-binding activity of LBP can be separated from the CD14-stimulatory activity, suggesting these activities are mediated by structural elements residing in different regions of the protein.

Acute-Phase Proteins↗

Reliability of the tear break-up time technique of assessing tear stability and the locations of the tear break-up in Hong Kong Chinese.

The measurement of tear break-up time (TBUT) in assessing stability of the tear film is somewhat controversial, even though the technique is widely used. We examined reliability of the technique within and among examiners and conclude that measurements of TBUT can be made reliably; full-beam observation of the cornea is preferable to scanning the cornea with a narrow slit in making the measurements. There may be differences in TBUT measurements made in the same subjects among examiners, but these differences are smaller with more experienced practitioners. In the Hong Kong Chinese (HK-Chinese), tear break-up appears to be more likely to first occur in the inferior periphery of the cornea. In this population mean TBUT is about 7.20 s; assuming a Gaussian distribution of TBUT values, 2.1 s should be adopted as the lower limit for normal TBUT in HK-Chinese.

Adolescent↗

Regulation of nitrogen fixation. Nitrogenase-derepressed mutants of Klebsiella pneumoniae.

1. A new procedure is described for selecting nitrogenase-derepressed mutants based on the method of Brenchley et al. (Brenchley, J.E., Prival, M.J. and Magasanik, B. (1973) J. Biol. Chem. 248, 6122-6128) for isolating histidase-constitutive mutants of a non-N2-fixing bacterium. 2. Nitrogenase levels of the new mutants in the presence of NH4+ were as high as 100% of the nitrogenase activity detected in the absence of NH4+. 3. Biochemical characterization of these nitrogen fixation (nif) derepressed mutants reveals that they fall into three classes. Three mutants (strains SK-24, 28 and 29), requiring glutamate for growth, synthesize nitrogenase and glutamine synthetase constitutively (in the presence of NH4+). A second class of mutants (strains SK-27 and 37) requiring glutamine for growth produces derepressed levels of nitrogenase activity and synthesized catalytically inactive glutamine synthetase protein, as determined immunologically. A third class of glutamine-requiring, nitrogenase-derepressed mutants (strain SK-25 and 26) synthesizes neither a catalytically active glutamine synthetase enzyme nor an immunologically cross-reactive glutamine synthetase protein. 4. F-prime complementation analysis reveals that the mutant strains SK-25, 26, 27, 37 map in a segment of the Klebsiella chromosome corresponding to the region coding for glutamine synthetase. Since the mutant strains SK-27 and SK-37 produce inactive glutamine synthetase protein, it is concluded that these mutations map within the glutamine synthetase structural gene.

Ammonia↗