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Biomedical subjects

R Ling

Publications and source records attributed to R Ling.

At least 37 records · Page 2Linked to original sources

Energy reflectance in the ear canal can exceed unity near spontaneous otoacoustic emission frequencies.

There is some controversy in the literature over whether the so-called "active mechanism" or "cochlear amplifier" is actually a power amplifier that can produce an output signal with more power than its input, or whether it simply minimizes dissipative losses within the cochlea without providing an actual power gain greater than unity. A corollary of this controversy is whether spontaneous otoacoustic emissions (SOAEs) represent the output of a nonlinear oscillator mechanism, i.e., a power amplifier which can produce an oscillatory output signal in the absence of an input oscillatory signal, or whether they represent the output of a noise-driven, passive, nonlinear system. This paper describes measurements of energy reflectance, and acoustic impedance in the ear canals of human subjects with strong SOAEs. The reflectance, and the resistive and reactive parts of the acoustic impedance, all show a frequency fine structure which correlates with SOAE frequencies, and which becomes more pronounced at low stimulus levels. In some ears at some SOAE frequencies, energy reflectance exceeds unity, and correspondingly, acoustic resistance is negative. This result demonstrates that there is a power gain at these frequencies: The power reflected from the cochlea to the ear canal exceeds the power incident. It is also consistent with the theory that these SOAEs are produced by a nonlinear oscillator mechanism in the cochlea.

Ear Canal↗

Double-evoked otoacoustic emissions. II. Intermittent noise rejection, calibration and ear-canal measurements.

Measurements of double-click-evoked otoacoustics emissions (2CEOAEs) and double-chirp distortion products (2ChDPs) are reported for normal-hearing adults based upon theory presented in an earlier report [Keefe, J. Acoust, Soc. Am. 103, 3489-3498 (1998)]. The nonlinear acoustic response of a probe assembly used in ear-canal measurements in tested in a calibration cavity to compare the double-evoked (2E) technique with existing OAE techniques. The 2E technique reduces the peak distortion by approximately 30 dB relative to existing click-evoked techniques. The 2E subtraction of click responses is partially analogous to current techniques in that the linear response is eliminated, but differs in that high-frequency measurements are improved by eliminating time gating of the cochlear response, and low-frequency measurements are improved by reducing probe distortion, especially when two acoustic sources are used. Because time gating is eliminated, it is straightforward to measure the onset of a click-evoked OAE. The nonlinear coherence function is used to measure the nonlinear distortion signal-to-noise ratio (DNR) for the 2ChDPs and 2CEOAEs. The DNR is typically 20-30 dB. An intermittent noise rejection technique is implemented in real time that compares a currently acquired ear-canal response with a stored response. Dissimilar responses indicate the presence of intermittent noise, and the noise-contaminated responses are thereby discarded before ensemble averaging.

Acoustic Stimulation↗

White-centred retinal haemorrhages (Roth spots).

Roth spots (white-centred retinal haemorrhages) were classically described as septic emboli lodged in the retina of patients with subacute bacterial endocarditis. Indeed many have considered Roth spots pathognomonic for this condition. More recent histological evidence suggests, however, that they are not foci of bacterial abscess. Instead, they are nonspecific and may be found in many other diseases. A review of the histology and the pathogenesis of these white-centred haemorrhages will be provided, along with the work-up of the differential diagnosis.

Endocarditis, Subacute Bacterial↗

A retrospective epidemiology study of contact eczema among the elderly attending a tertiary dermatology referral centre in Singapore.

AIM: The aim of this study was to examine the epidemiology of contact eczema in the elderly patients attending a skin clinic in Singapore. METHODOLOGY: This is a retrospective study on patients attending our skin clinic at the National Skin Centre. All patients older than 49 years old attending our Contact and Occupational Dermatoses Clinic between 1990 and 1993 were included in the study. The prevalence of contact eczema among different age groups (50-59 years, 60-69 years, and 70-79 years) were compared. Diagnosis of contact dermatitis was based on the clinical history, physical examination and relevant patch test reactions. Demographic data of the patients were collected and analysed. Chi-square test was used for statistical analysis. RESULTS: Two hundred and one patients who were older than 49 years old, were included in the study. There was no significant difference in the prevalence of personal history of atopy among the 3 age groups. There was no significant difference in the racial distribution of the 3 age groups. The proportion of patients who were occupationally active decreased with age (50% vs 23% vs 0% respectively). There was no significant difference in the proportion of patients with positive patch test reactions in the 3 age groups although the proportion appears to increase with age (68% vs 75% vs 75% respectively). Similarly, the proportion of patients with allergic contact dermatitis was slightly higher in the older age group although the difference was not statistically significant among the 3 age groups (32% vs 45% vs 39% respectively). The face (54%) and hands (31%) were the commonest sites of eczema in the younger age group (50-59 years age group) whereas the lower limbs (41%) and the upper limbs (33.3%) were the commonest sites of eczema in the older patients (70-79 years age group). Nickel allergy was significantly more common in the younger age group (23% vs 17% vs 14% respectively). Medicament allergy (clioquinol-mix) and medicament related allergens e.g. balsam of Peru and fragrance-mix and para-phenylenediamine were slightly more prevalent in the older patients. CONCLUSIONS: The findings appear to indicate that the prevalence of allergic contact dermatitis is higher in older patients and that contact dermatitis tends to occur on the extremities in older patients than younger patients.

Aged↗

Production of hepatitis B virus covalently closed circular DNA in transfected cells is independent of surface antigen synthesis.

Covalently closed circular DNA (cccDNA) is the first hepatitis B virus (HBV) DNA replicative intermediate formed from the genomic DNA and serves as the template for synthesis of viral mRNA and pregenomic RNA. It also appears to be produced by intracellular recycling of relaxed circular DNA intermediates. Here, we report that none of the forms of HBV surface antigen affect this intracellular recycling of HBV DNA. Elimination of the initiation codons for the large and middle surface proteins did not affect the detection of surface antigen in culture supernatants. In contrast, detection of surface antigen was eliminated by the removal of, or the introduction of two stop codons downstream of, the initiation codon of the small (major) surface antigen. None of the mutations affected the production, in transfected HepG2 cells, of HBV DNA replicative intermediates, including cccDNA.

Cell Line↗

Selection of mutations in the hepatitis B virus polymerase during therapy of transplant recipients with lamivudine.

We describe mutations in the hepatitis B virus (HBV) polymerase gene in viruses which reactivated in two patients during therapy with -2'-deoxy-3'-thiacytidine, or lamivudine (3TC), and following orthotopic liver transplantation for chronic hepatitis B. Virus resistance to 3TC is associated with mutations which lead to amino acid substitutions in the highly conserved tyr-met-asp-asp (YMDD) motif, part of the active site of the polymerase, and which parallel those seen in resistant human immunodeficiency virus (HIV). Substitutions of valine and isoleucine for methionine were found in the two cases. The significance of single secondary mutations, which differ between viruses from the two patients, remains to be determined. Thus, viral resistance to lamivudine of hepatitis B virus mimics that of HIV and can occur in the setting of immunosuppression after liver transplantations.

Adult↗

Sequence of the nucleocapsid protein gene of subgroup A and B avian pneumoviruses.

The nucleocapsid protein (N) gene of two subgroup A and one subgroup B strains of avian pneumovirus has been cloned and sequenced. The gene of all three isolates comprised 1197 nucleotides (nt), which formed a single major open reading frame, potentially encoding a protein of 391 amino acid residues. The N gene of the two subgroup A isolates differed by only 1 nt but differed by 282 (24%) nt and 35 (11%) amino acids from the B isolate. The predicted protein was identical in length to that of human, bovine and ovine respiratory syncytial viruses, the amino acid identity being approximately 41% overall but with some regions of identity > 90%.

Amino Acid Sequence↗

Sequence and in vitro expression of the phosphoprotein gene of avian pneumovirus.

The phosphoprotein (P) gene of two subgroup A strains of avian pneumovirus comprised 855 nucleotides containing only one substantial open reading frame encoding a protein of 278 amino acids, with a predicted M(r) of 30,323. In vitro translation of P mRNA in a wheat germ system resulted in the synthesis of two polypeptides of M(r) 35,000. Comparison of the deduced P protein sequence with that of the known mammalian pneumoviruses revealed overall amino acid identities ranging from 31 to 34.5%, suggesting a distant relationship. However, there was a much higher identity (63.2-68.4%) in a region of 57 residues, which included a heptad repeat sequence.

Amino Acid Sequence↗

Case report: malignant fibrous histiocytoma following radiation therapy of fibrous dysplasia.

Malignant fibrous histiocytoma commonly occurs spontaneously. In some cases it follows previous therapeutic or incidental irradiation, or miscellaneous pre-existing osseous conditions. Recently, it has been associated with total hip arthroplasty. We report a case of malignant fibrous histiocytoma following radiation therapy of fibrous dysplasia and review the relevant literature.

Bone Neoplasms↗

Use of single-cysteine mutants to probe the location of the disulfide bond in LamB protein from Escherichia coli.

The two cysteine residues of the LamB protein of Escherichia coli outer membrane have been shown to form an intrasubunit disulfide whose location differs greatly in the two current topology models of the LamB protein. This study probes the location of the disulfide by examining conditions for intersubunit disulfide formation in single-cysteine mutants of LamB protein. Formation of an intersubunit bond in the purified mutant proteins, which resulted in a disulfide-linked dimer, only occurred after heat treatment, suggesting the disulfide is not exposed on the surface in the native protein.

Bacterial Outer Membrane Proteins↗

Effect of cup geometry and the presence of cement on acetabular component fixation.

Two series of implanted conical, polyethylene Ring cups were studied clinically and radiographically. In one series the cups were uncemented while in the second cement was used. The results using cemented conical cups were then compared with results using a cemented cup of hemispherical design to study the effect of cup geometry. At 7-8 years a total of 3.8% of the cemented conical series and 2.9% of the uncemented were revised for aseptic loosening. At 9 years survivorship was identical. Migration of the sockets occurred in approximately 25% of both series and was directly related to cup cover of less than 80% (P < 0.001). The series of cemented hemispherical cups were reviewed after an identical period. Although the numbers revised for loosening were comparable in this and the cemented conical group, radiological migration was statistically greater in the latter (P < 0.001). Alternative methods of socket preparation and cement technique were thought to be the most likely explanation for the observed differences.

Acetabulum↗

Sequence analysis of the 22K, SH and G genes of turkey rhinotracheitis virus and their intergenic regions reveals a gene order different from that of other pneumoviruses.

The nucleotide and deduced amino acid sequences of three genes of turkey rhinotracheitis virus (TRTV) together with the nucleotide sequences of the relevant intergenic regions were determined. The deduced amino acid sequence of one of the genes shows significant identity (42%) to that of the 22K protein of human respiratory syncytial virus (RSV). The TRTV 22K gene, like that of RSV, has a second open reading frame, although the amino acid sequence deduced from this reading frame does not show any similarity to the equivalent predicted RSV protein. The other two genes and their deduced amino acid sequences do not show any sequence similarity to the genes of other pneumoviruses. However, the hydrophobicity profiles of the predicted proteins do show similarities to those of the small hydrophobic (SH) and attachment protein (G) genes of RSV. The TRTV G gene is 1193 nucleotides in length and encodes a protein of 391 amino acids (M(r) 42984), which is rather larger than the RSV G protein (predicted M(r) 36000). The TRTV SH gene is 589 nucleotides in length, encoding a protein of 174 amino acids (M(r) 18797), which is considerably larger than the size of the RSV SH protein (M(r) 7500). The sequences of the intergenic regions derived from clones of polycistronic mRNAs and polymerase chain reaction products obtained with primers from different genes reveal the order on the virus genome to be 3' F-22K-SH-G 5'. This differs from the gene order of paramyxoviruses and morbilliviruses, which lack a 22K gene (and in some cases a SH gene), and the pneumoviruses RSV and pneumonia virus of mice, which have the F and 22K genes located after the G gene.

Amino Acid Sequence↗

Method to measure acoustic impedance and reflection coefficient.

A frequency-domain based system for measuring acoustic impedance and reflection coefficient is described. The calibration procedure uses a least-mean-squares approximation to the Thevenin parameters describing the source and receiver characteristics in which the data measured on closed, cylindrical tubes are matched to a viscothermal tube model. The system is intended for use in acoustical measurement in human ear canals, in which the cross-sectional area of the ear canal at the point of insertion is imprecisely known. This area is acoustically estimated from the impedance data, and the reflection coefficient is calculated in terms of this area and the impedance data. Measurements on a variety of closed tubes show the method is accurate over the frequency range investigated (less than 10.7 kHz). The time-domain reflection function is evaluated by transforming the reflection coefficient from the frequency domain, but the finite bandwidth of the measured data limits the accuracy of time-domain response measurements. The method is well suited for frequency-domain measurements in human ear canals.

Acoustic Impedance Tests↗

Role of a disulfide bond in the thermal stability of the LamB protein trimer in Escherichia coli outer membrane.

In order to understand the unusual heat resistance of LamB protein (the outer membrane component of the maltose transport system in Escherichia coli and its receptor for bacteriophage lambda), we investigated the role of its 2 cysteinyl residues. Our studies show that Cys22 and Cys38 form an intrasubunit disulfide bond which contributes to the heat stability of the LamB protein trimer. Physical evidence for the disulfide was obtained by using site-directed mutagenesis to convert Asn36 to Met, which allowed cyanogen bromide cleavage between the 2 cysteines. Upon reduction one of the N36M fragments migrated as two pieces, resolved by two-dimensional polyacrylamide gel electrophoresis. Other mutagenized LamB proteins, in which 1 or both Cys residues were converted to Ser, exhibited a sharp loss of thermal stability. In contrast to wild-type LamB protein trimer, which does not dissociate to monomers even after 60 min at 100 degrees C, only 10-15% of the mutant LamB proteins remain trimeric after boiling 10 min. The disulfide bond in LamB protein is not required for its transport function, since both mutagenized LamB protein and N-ethylmaleimide-labeled LamB protein exhibit normal uptake of sugars in proteoliposomes. Finally, the disulfide bond must not be between subunits of the LamB trimer since reversible dissociation of trimer is achieved by low pH or denaturants in the absence of reducing agent.

Amino Acid Sequence↗

A comparison of the effects of various stimulatory agents on t-PA secretion by normal and malignant cell lines.

Succinyl con A and acetyl con A both stimulated epithelial cells to produce similar yields of tissue plasminogen activator (t-PA) to those previously obtained with native con A. However, unlike con A, the derivatized lectins did not adversely affect cell morphology and viability, and cells treated with succinyl con A could secrete t-PA for a prolonged period. Con A and the two derivatives produced similar morphological effects in Bowes melanoma cells, but t-PA production was not increased. Elevated cyclic nucleotide concentrations did not affect t-PA production from epithelial cells, but calcium ionophore treatment generated t-PA yields similar to those obtained with lectins. Azacytidine, which enhanced t-PA production from epithelial cells, did not increase yields from Bowes melanoma cells, and also sodium butyrate, reported to increase t-PA yields from human endothelial cells, had no effect on either cell line.

Azacitidine↗