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Biomedical subjects

S Chu

Publications and source records attributed to S Chu.

At least 127 records · Page 7Linked to original sources
PubMed1994

Intra-epithelial palatine nerve endings and their regulation of ciliary activity of frog palate epithelium.

1. Direct contact between intra-epithelial nerve endings and ciliated cells was observed in frog (Rana pipiens) palate epithelium. 2. Electrical stimulation of the palatine nerve to the explant or the explant culture induced an increase in ciliary beat frequency in explant and outgrowth cells. 3. Atropine inhibited electrically stimulated ciliary beat frequency increase in the explant and outgrowth cells. 4. Gap junctional intercellular communication appears to be involved in the propagation of stimulated ciliary beat frequency increase from innervated to non-innervated ciliated cells.

Animals↗
PubMed1993

Single- and multiple-dose pharmacokinetics of clarithromycin, a new macrolide antimicrobial.

The pharmacokinetics of clarithromycin and its active 14(R)-hydroxy metabolite were evaluated after single and multiple oral doses of 250 and 500 mg of clarithromycin. Multiple-dose regimens used 12-hour dosing intervals for 7 doses. Plasma and urine concentrations were measured using high-performance liquid chromatography. Appearance of clarithromycin and its metabolite in plasma were rapid, as reflected by mean times to maximum plasma concentration ranging from 1.8 to 2.6 and 1.8 to 2.9 hours, respectively. The rises in clarithromycin peak plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) were disproportionate to increase in dose, suggesting nonlinearity in parent compound pharmacokinetics. Clarithromycin terminal disposition half-life (t1/2) also exhibited dose dependency, ranging from harmonic means of 2.7 to 4.8 hours. In contrast, based on Cmax AUC, and predicted/observed accumulation ratios, nonlinearity in metabolite pharmacokinetics was not observed. Plasma accumulation of metabolite occurred to a much lesser degree than that of the parent compound despite a substantially longer t1/2 for the metabolite (metabolite accumulation ratios based on AUC dose 7/AUC dose 1:250-mg regimen = 1.03 +/- 0.33, 500-mg regimen = 0.81 +/- 0.29, parent accumulation ratios: 250-mg regimen = 1.64 +/- 0.47, 500-mg regimen = 1.65 +/- 0.69). This would suggest that formation of this metabolite is capacity-limited and that this may in part account for the nonlinearity observed in clarithromycin pharmacokinetics. Urinary excretion constituted a relatively important route of elimination of clarithromycin, with renal clearance accounting for 17 to 31% of apparent total body clearance.

Administration, Oral↗
PubMed1993

Force on single actin filaments in a motility assay measured with an optical trap.

We have used an optical trap to measure or exert a force on single actin filaments via the attachment of polystyrene beads which were coated with NEM-modified HMM. In the simplest experiment, beads were attached to rhodamine phalloidin labelled actin filaments and observed to move on an HMM coated surface in the presence of ATP. Moving beads were steered into the vicinity of the trap using a PZT operated microscope stage. The minimum force needed to stop a moving bead was measured by lowering the trap strength until the bead resumed movement. By aligning the optical trap with the centre of a quadrant detector placed in an image plane of the microscope, it was possible to measure the force exerted on a filament by measuring the displacement of the bead position from the centre of the trap. In each of these experiments, the trap was calibrated by applying a Stokes force to a bead in free solution. The characteristics of the trap were studied, and the displacement of the bead from the centre of the trap was shown to be directly proportional to the applied force over a large part of the total range of the trap. The compliance of the trap could be substantially reduced by the use of feedback control to deflect the laser beam via an acousto-optic modulator. The advantages and limitations of this technique will be discussed.

Actin Cytoskeleton↗
PubMed1993

Calcitonin increases transcription of parathyroid hormone-related protein via cAMP.

Transcriptional regulation of the human parathyroid hormone-related protein (PTHrP) gene by calcitonin was examined in a lung cancer line (BEN cells). Northern analysis demonstrated that calcitonin caused a rapid 4.5-fold elevation in PTHrP mRNA. Transient transfection of a construct containing 1119 base pairs of the human PTHrP gene 5' to the ATG start site of translation, fused to the CAT reporter sequence, was used to demonstrate a five-fold increase in transcription by calcitonin. Similar increases were also observed when transfected cells were exposed to a number of cAMP agonists including forskolin, as well as isobutyl-methylxanthine. A putative cAMP responsive element (5'-TGACTTCA-3') present within exon 4 was placed upstream of the heterologous SV40 promoter. Expression of this construct was elevated 4.5-fold in response to calcitonin and 7-fold in response to forskolin. Similar responses to calcitonin occurred with a smaller construct (pZMR30) containing 530 bp of sequence upstream of the ATG start site. Thus we postulate that calcitonin acts at least partially via cAMP through this element in exon 4 of the human PTHrP gene.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Gain of function mutations in p53.

We report that the expression of murine or human mutant p53 proteins in cells with no endogenous p53 proteins confers new or additional phenotypes upon these cells. Mutant p53 proteins expressed in cell lines lacking p53 resulted in either enhanced tumorigenic potential in nude mice ((10)3 cells) or enhanced plating efficiency in agar cell culture (human SAOS-2 cells). Also, mutant human p53 alleles, unlike the wild-type p53 protein, could also enhance the expression of a test gene regulated by the multi-drug resistance enhancer-promoter element. These data demonstrate a gain of function associated with p53 mutations in addition to the loss of function shown previously to be associated with mutations in this tumour suppressor gene.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Kennedy's disease: genetic diagnosis of an inherited form of motor neuron disease.

Kennedy's disease (X-linked spinal and bulbar muscular atrophy) is an inherited form of motor neuron disease that may be diagnosed genetically using the polymerase chain reaction (PCR). This form of motor neuron disease principally affects the proximal limb girdle muscles as well as those involved with deglutition and phonation. Onset is usually late, in the fourth to fifth decades of life, and progression is slow. Moderate gynaecomastia and testicular atrophy are usually present, suggesting a defect in androgen receptor function. Being inherited in an X-linked recessive manner, only males are affected, with females as the unaffected carriers. The genetic abnormality that causes Kennedy's disease is an enlargement of the androgen receptor (AR) gene, which is located on the proximal long arm of the X chromosome. In patients with this disease, a region in the gene containing repeated CAG triplet nucleotides is approximately twice the size of that found in normal people. Using PCR to amplify this region of the AR gene, this study confirms this genetic mutation in 12 males from eight different families. All these families live on the east coast of Australia. This mutation was not found in five patients with other forms of motor neuron disease. Twelve heterozygote females, the daughters of affected males and carrier females, have also been identified. In addition, there are 14 asymptomatic and as yet untested sons of carriers, ranging in age from less than one year to over 40 years of age. Each has a 50% chance of inheriting the abnormal gene from his mother and thus developing Kennedy's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

An Aeromonas salmonicida gene which influences a-protein expression in Escherichia coli encodes a protein containing an ATP-binding cassette and maps beside the surface array protein gene.

A conserved Aeromonas salmonicida gene (abcA) affecting expression of the surface array protein gene (vapA) in Escherichia coli was identified. The 924-bp gene starts 205 bp after vapA and codes for a protein with a deduced molecular weight (M(r)) of 34,015 containing an N-terminal P-loop and significant homology to the ATP-binding cassette transport protein superfamily. AbcA was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) by using T7 polymerase expression and DNA-directed translation and was copurified with the sarkosyl-soluble cytoplasmic membrane fraction. The protein displayed aberrant migration during SDS-PAGE. A lacZ fusion containing 128 bp of upstream sequence and 387 bases in the 5' end of abcA was constructed, and the beta-galactosidase activity of the abcA-lacZ fusion gene was shown to be similar in E. coli and A. salmonicida. The 130,000-M(r) AbcA-LacZ fusion protein was purified, and by using an ATP affinity column, the 129 AbcA N-terminal P-loop-containing residues were shown to bind ATP.

ATP-Binding Cassette Transporters↗
PubMed1993

Transcriptional analysis of the Aeromonas salmonicida S-layer protein gene vapA.

The vapA gene of Aeromonas salmonicida encodes the subunit of the surface protein array known as A-layer. Nucleotide sequence analysis of the 374 bp of DNA immediately upstream of vapA revealed two potential promoter sequences and other possible regulatory sequences. Sequencing and polymerase chain reaction analysis showed that the region was conserved in wild-type A. salmonicida. Primer extension and Northern (RNA) blot analysis showed that vapA transcription in A. salmonicida was directed predominantly by a distal promoter, P1, resulting in a 1.7-kb unit-length mRNA with an untranslated 181-nucleotide leader sequence which contained two predicted low-free-energy stem-loop structures. Northern analysis of cells grown at 15 degrees C showed that vapA transcript production peaked during the mid-log phase of growth (A600 = 0.25). At 15 degrees C, the half-life of the vapA mRNA was 22 min, while at 20 degrees C, the half-life was significantly shorter, 11 min. The amount of vapA transcript produced was reduced by growth in the presence of the DNA gyrase inhibitors nalidixic acid and novobiocin. Environmental factors such as growth temperature and atmospheric oxygen tension also affected the quantity of vapA mRNA. vapA transcript could not be detected in mutants which produced either low levels of full-length or truncated A protein or no detectable A protein.

Aeromonas↗
PubMed1993

Related individuals with different androgen receptor gene deletions.

We have identified different members of one family affected by androgen insensitivity syndrome who have deletions of different exons of the X-linked androgen receptor (AR) gene. Two affected (XY) siblings have a deletion of exon E of the AR gene and their affected (XY) aunt has a normal exon E, but a deletion of exons F and G of the same gene. The mother and maternal grandmother of the children both carry the exon E deletion, but not the exon F, G deletion. Both deletions are 5 kb in length and have one breakpoint within a 200-bp region in intron 5; however, they extend in opposite directions. The probability that these two different deletions have arisen at random is extremely low, but the cause of this intriguing phenomenon remains to be found.

Adult↗