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Biomedical subjects

C M Chow

Publications and source records attributed to C M Chow.

At least 19 recordsLinked to original sources
PubMed2001

Vascular endothelial function in cyclosporine and tacrolimus treated renal transplant recipients.

BACKGROUND: Endothelial dysfunction is an early key event in the development of arteriosclerotic cardiovascular disease (ASCVD), thus an early marker of subclinical ASCVD. Endothelial function is impaired in renal transplant recipients (RTR) treated with cyclosporine (CyA). Tacrolimus is associated with less hyperlipidemia and hypertension than CyA, however, there are no data on endothelial function in tacrolimus-treated RTR. METHODS: High-resolution brachial ultrasonography was used to assess endothelium-dependent dilatation (EDD), and endothelium-independent dilatation (EID) in 20 stable RTR and a control group of 10 healthy subjects without clinical evidence of ASCVD. The RTR group included patients receiving CyA (n=10) and tacrolimus (n=10). EDD and EID were measured as percent increase in brachial artery diameter in response to reactive hyperemia and nitroglycerin, respectively. RESULTS AND CONCLUSIONS: EDD was significantly lower in RTR versus controls (1.7+/-0.7 vs. 7.3+/-0.7%, P<0.0001), whereas EID was similar in the two groups. No significant differences were found in EDD or in EID between CyA- and tacrolimus-treated RTR. Glomerular filtration rate, plasma homocysteine, blood pressure, and lipid profiles were similar in CyA- and tacrolimus-treated RTR.

Adult↗
PubMed2001

Paradoxic decrease in ischemic mitral regurgitation with papillary muscle dysfunction: insights from three-dimensional and contrast echocardiography with strain rate measurement.

BACKGROUND: Ischemic mitral regurgitation (MR) was first ascribed to papillary muscle (PM) contractile dysfunction. Current theories include apical leaflet tethering caused by left ventricular (LV) distortion, but PM dysfunction is still postulated and commonly diagnosed. PM contraction, however, parallels apical tethering, suggesting the hypothesis that PM contractile dysfunction can actually diminish MR due to ischemic distortion of the inferior base alone. METHODS AND RESULTS: We therefore occluded the proximal circumflex circulation in 7 sheep while maintaining PM perfusion, confirmed by contrast echocardiography. By 3D echocardiography, we measured the tethering distance between the ischemic medial PM tip and anterior annulus and LV ejection volume to give MR (by subtracting flowmeter LV outflow). In 6 sheep without initial MR, inferior ischemia alone produced PM tip retraction with restricted leaflet closure and mild-to-moderate MR (regurgitant fraction, 25.2+/-2.8%). Adding PM ischemia consistently decreased MR and tethering distance (5.2+/-0.3 to 1.4+/-0.3 mL; +3.8+/-0.5 mm to -2.2+/-0.7 mm axially relative to baseline; P<0.001) as PM strain rate decreased from +0.78+/-0.07 per second (contraction) to -0.42+/-0.06 per second (elongation, P<0.001) and leaflet tenting decreased. In one sheep, prolapse and MR resolved with inferior ischemia and recurred with PM ischemia. CONCLUSIONS: PM contractile dysfunction can paradoxically decrease MR from inferobasal ischemia by reducing leaflet tethering to improve coaptation. This emphasizes the role of geometric factors in ischemic MR mechanism and potential therapy.

Animals↗
PubMed2001

Chordal cutting: a new therapeutic approach for ischemic mitral regurgitation.

BACKGROUND: Mitral regurgitation (MR) conveys adverse prognosis in ischemic heart disease. Because such MR is related to increased leaflet tethering by displaced attachments to the papillary muscles (PMs), it is incompletely treated by annular reduction. We therefore addressed the hypothesis that such MR can be reduced by cutting a limited number of critically positioned chordae to the leaflet base that most restrict closure but are not required to prevent prolapse. This was tested in 8 mitral valves: a porcine in vitro pilot with PM displacement and 7 sheep with acute inferobasal infarcts studied in vivo with three-dimensional (3D) echo to quantify MR in relation to 3D valve geometry. METHODS AND RESULTS: In all 8 valves, PM displacement restricted leaflet closure, with anterior leaflet angulation at the basal chord insertion, and mild-to-moderate MR. Cutting the 2 central basal chordae reversed this without prolapse. In vivo, MR increased from 0.8+/-0.2 to 7.1+/-0.5 mL/beat after infarction and then decreased to 0.9+/-0.1 mL/beat with chordal cutting (P<0.0001); this paralleled changes in the 3D leaflet area required to cover the orifice as dictated by chordal tethering (r(2)=0.76). CONCLUSIONS: Cutting a minimum number of basal chordae can improve coaptation and reduce ischemic MR. Such an approach also suggests the potential for future minimally invasive implementation.

Animals↗
PubMed2001

Assault by burning--a reappraisal.

Assault by burning is a serious form of trauma that often results in higher incidence of inhalation injury, longer intensive care unit (ICU) and hospital stay, and higher mortality rate than is observed in the general burn population. We evaluated the epidemiology and outcome of assault burn victims treated in a tertiary burn center over a 6-year period. Among the 1063 acute burn patients who had been admitted to the Burns Unit between March 1993 and February 1999, 28 (2.6%) had assault burn injuries either by scald, chemical or fire. The mean extent of burn was 21.9%+/-20.8% (range 2-90%) total body surface area and the mean length of hospital stay was 65.2+/-107.3 days (range 1-565). Nineteen out of 25 patients (67.9%) underwent 76 operations. Nine patients had inhalation injuries requiring intubation and ICU admission. Three patients died in the series, which yielded a mortality rate of 10.7%. Compared to the general burn population, the assault burn group had significantly larger burn size (P<0.001), higher incidence of inhalation injury (P<0.001), longer ICU and hospital stay (P<0.001), and higher mortality rate (P<0.005). When these 28 victims were grouped according to the type of assault burn injury into a fire group, chemical group and scald group, all the 9 ICU admission and the 3 mortalities belonged to the fire group. Assault by fire resulted in larger burn size (P=0.03), more inhalation injury (P<0.001) and longer ICU stay (P=0.02). Although the fire group had a longer hospital stay and higher mortality rate, this was statistically insignificant.

Adolescent↗
PubMed2001

Relationship between the size of neopharynx after laryngectomy and long-term swallowing function: an assessment by scintigraphy.

OBJECTIVES: To study the relationship between the size of neopharynx after total laryngectomy and long-term swallowing function by means of scintigraphy. STUDY DESIGN: The width of pharyngeal remnant was measured during surgery in 11 patients. Their swallowing function was assessed by scintigraphy 8 to 10 years after surgery. METHODS: The width of pharyngeal remnant at its narrowest point in both relaxed and stretched state was measured during surgery. Postoperative scintigraphy data on swallowing were obtained and computed along 3 lines, (1) transit time through neopharynx, (2) percentage of bolus transferred, and (3) swallowing efficiency. The relationship between the 2 sets of data was analyzed by linear regression analysis. RESULTS: (1) No statistically significant relationship was found between the size of neopharynx and swallowing function. (2) All patients are clinically asymptomatic. CONCLUSIONS: The swallowing function is not affected by the size of the neopharynx in 11 patients with pharyngeal remnant width ranging from 3 to 8 cm (stretched).

Aged↗
PubMed2001

Expectant treatment of ectopic pregnancies: clinical and sonographic predictors.

OBJECTIVE: We identified the potential clinical and sonographic predictors of the spontaneous resolution of ectopic pregnancies. SUBJECTS AND METHODS: We performed a prospective study of 78 consecutive patients with a transvaginal sonographic diagnosis of ectopic pregnancy who had either two consecutive quantitative measurements of their beta subunit of human chorionic gonadotropin (beta-hCG) more than 24 hrs apart or an embryo with a heart beat. We evaluated the patient's age, time from the last menstrual period, beta-hCG level, size of ectopic pregnancy, presence of a gestational sac or embryonic elements, vascularity on color Doppler sonography, peak systolic velocity, and resistive index of ectopic pregnancy at the time of presentation as potential independent predictors of the final outcome. Logistic regression was performed to identify the independent predictors. RESULTS: Forty-six patients had declining beta-hCG levels, and 32 ectopic pregnancies showed an embryo with a heart beat or had steady or rising beta-hCG levels. Univariate analysis indicated that a longer time from the last menstrual period (older ectopic pregnancies), lower beta-hCG levels, and the absence of gestational sac are statistically more significantly seen in ectopic pregnancies with declining beta-hCG levels (p < 0.05). Resistive index of ectopic pregnancy reached borderline significance (p = 0.05). In a multiple logistic model, the same variables were independent predictors of outcome (p < 0.05). Resistive index was also a predictor (p = 0.09). CONCLUSION: Longer times from the last menstrual period, lower beta-hCG levels, absence of gestational sacs, and higher resistive indexes of ectopic pregnancy at the time of presentation appear to be independent predictors of the spontaneous resolution of ectopic pregnancy.

Adult↗
PubMed2000

Transcription factor dosage affects changes in higher order chromatin structure associated with activation of a heterochromatic gene.

The mechanisms of transcriptional activation in heterochromatin were investigated by using FISH to directly visualize changes in chromatin organization during activation of a heterochromatic lambda5 transgene. A DNase I hypersensitive site was shown to relocate the transgene to the outside of the pericentromeric heterochromatin complex in the absence of transcription. Activation of transcription, which is dependent on the transcription factor EBF, occurs in a stochastic manner that resembles telomeric silencing in yeast, with the transcribed gene remaining closely associated with the heterochromatin complex. Reducing the dosage of EBF results in a reduced frequency of localization of the transgene to the outside of the heterochromatin complex and lower levels of transcription. These data provide evidence that transcription factors can initiate changes in higher order chromatin structure during the earliest stages of gene activation.

Animals↗
PubMed2000

Transmitral Doppler: a new transthoracic contrast method for patent foramen ovale detection and quantification.

OBJECTIVES: This study compared a new transthoracic echocardiographic (TTE) method for detection of right to left bubble passage, transmitral Doppler (TMD), against two-dimensional (2D) TTE contrast study and the gold standard, of transesophageal echocardiography (TEE), and assessed its utility in quantitative assessment of patent foramen ovales (PFO). BACKGROUND: Current TTE methods are relatively insensitive in PFO detection and do not allow quantitative assessment of right to left shunt. METHODS: In 44 patients (59 years, range 34 to 76 years) saline contrast and color Doppler studies were performed in three conditions--TTE TMD, TTE 2D and TEE. Bubble transit on the TMD was measured semiquantitatively by a visual bubble score and objectively by integrating the acoustic power within the mitral velocity envelope. RESULTS: By TEE it was determined that 17 patients (39%) had PFOs; 16 had right to left contrast passage, and only 1 had left to right flow by color Doppler. Against TEE contrast study, the sensitivity of TMD and 2D contrast studies were 100% and 75%, respectively, with specificity of 96% and 100%. Greater than 10 bubbles on a single beat of the resting contrast TMD identified patients with a maximum resting TEE PFO opening diameter >2 mm with 78% sensitivity and 100% specificity. There was a strong correlation (r2 = 0.72, p<0.01) between the TMD acoustic power and PFO opening diameter. CONCLUSIONS: Transmitral Doppler is a sensitive and specific method for TTE PFO detection that allows quantification of right to left bubble passage and may obviate the need for TEE in many patients after stroke.

Adult↗
PubMed2000

Conservation of heterochromatin protein 1 function.

Heterochromatin represents a cytologically visible state of heritable gene repression. In the yeast, Schizosaccharomyces pombe, the swi6 gene encodes a heterochromatin protein 1 (HP1)-like chromodomain protein that localizes to heterochromatin domains, including the centromeres, telomeres, and the donor mating-type loci, and is involved in silencing at these loci. We identify here the functional domains of swi6p and demonstrate that the chromodomain from a mammalian HP1-like protein, M31, can functionally replace that of swi6p, showing that chromodomain function is conserved from yeasts to humans. Site-directed mutagenesis, based on a modeled three-dimensional structure of the swi6p chromodomain, shows that the hydrophobic amino acids which lie in the core of the structure are critical for biological function. Gel filtration, gel overlay experiments, and mass spectroscopy show that HP1 proteins can self-associate, and we suggest that it is as oligomers that HP1 proteins are incorporated into heterochromatin complexes that silence gene activity.

Amino Acid Sequence↗
PubMed1998

Transesophageal echocardiography for ascending aortic dissection: is it enough for surgical intervention?

BACKGROUND: Acute ascending aortic dissection is a surgical emergency that requires expeditious diagnosis and prompt surgical intervention. In many centers, transesophageal echocardiography (TEE) is the test of choice on which surgical decisions are based. Echocardiographic false-positive diagnoses are rare but can occur with potentially severe consequences. CASE REPORT: Two clinical cases where ascending aortic dissections were falsely diagnosed by TEE are presented. DISCUSSION: Recent literature comparing the diagnostic accuracy of TEE and other imaging techniques are reviewed. Anatomical limitations of TEE and potential causes of false-positive results are discussed. Multiplane probe reduces, but does not eliminate, the occurrence of false-positive findings. To improve diagnostic specificity without undue delays in the course of clinical decision making, we recommend dividing positive TEE findings into "definite" and "probable" categories. Such subclassification is helpful in identifying cases where additional confirmatory tests are desirable in situations of uncertain diagnosis.

Adult↗
PubMed1996

Correlation of exons with functional domains and folding regions in a cellulase from Agaricus bisporus.

The cellulase gene cel3 has been isolated from Agaricus bisporus and sequenced. The 5'-end of the cel3 transcript was determined by primer extension and S1 nuclease protection. Putative regulatory elements have been identified in the cel3 promoter and 3'-untranslated regions. The cel3 coding region is interrupted by six short introns, two of which separate the coding regions for the three modules in the CEL3 protein: cellulose-binding domain, linker region, and catalytic domain. Three of the remaining four introns are positioned in regions coding for loops between structural moieties. Intron positions are conserved between cel3 and other related cellulases.

Agaricus↗
PubMed1995

Sequence of the met-10+ locus of Neurospora crassa: homology to a sequence of unknown function in Saccharomyces cerevisiae chromosome 8.

We have determined the sequence of the Neurospora crassa met-10+ gene and its flanking regions, and have isolated and analyzed cDNA clones for this region. We have identified two closely linked genes transcribed in the same orientation. The met-10+ gene is the downstream gene; an open reading frame (ORF) derived from five exons encodes a 475-amino-acid protein. The deduced protein lacks similarity to other characterized proteins. However, it exhibits a strong similarity to the product of an ORF of unknown function on Saccharomyces cerevisiae chromosome 8. This sequence similarity suggests functional equivalence and should facilitate identification of the function of met-10+ using gene disruptions in S. cerevisiae.

Amino Acid Sequence↗
PubMed1994

Effects of REM sleep on the ventilatory response to airway occlusion in the dog.

We determined the effects of sleep state on the ventilatory response following transient airway occlusion and on the response to vagal blockade in the unanesthetized sleeping dog. Three tracheotomized dogs underwent repeated occlusions (159 trials) during rapid eye movement (REM) and nonrapid eye movement (NREM) sleep. In all sleep states we found significant but variable transient hyperventilation following release of occlusion. In NREM sleep, a significant central apnea [expiratory time (TE) prolonged 2-10 times control] followed the hyperpneic response, so long as the increase in tidal volume (VT) during the hyperpnea exceeded three times control VT, that is, a volume-dependent apneic threshold. In REM sleep with maintained levels of eye movement density, hyperventilation commonly followed release of obstruction but only very rarely did VT exceed the volume threshold, and central apnea was rare. Cervical vagal blockade was used to show that significant inhibitory pulmonary stretch receptor reflexes were present in both NREM and REM sleep, although the strength of the reflex was diminished in REM. We postulate that the phasic events of REM sleep inhibit the increase in VT in response to the chemical stimuli accumulated during airway occlusion and also interfere with the prolongation of TE in response to lung stretch and/or transient hypocapnia. The result is that central apnea occurs only very rarely in REM sleep.

Airway Obstruction↗
PubMed1994

The cel3 gene of Agaricus bisporus codes for a modular cellulase and is transcriptionally regulated by the carbon source.

A 52-kDa protein, CEL3, has been separated from the culture filtrate of Agaricus bisporus during growth on cellulose. A PCR-derived probe was made, with a degenerate oligodeoxynucleotide derived from the amino acid sequence of a CEL3 CNBr cleavage product and was used to select cel3 cDNA clones from an A. bisporus cDNA library. Two allelic cDNAs were isolated. They showed 98.8% identity of their nucleotide sequences. The deduced amino acid sequence and domain architecture of CEL3 showed a high degree of similarity to those of cellobiohydrolase II of Trichoderma reesei. Functional expression of cel3 cDNA in Saccharomyces cerevisiae was achieved by placing it under the control of a constitutive promoter and fusing it to the yeast invertase signal sequence. Recombinant CEL3 secreted by yeast showed enzymatic activity towards crystalline cellulose. At long reaction times, CEL3 was also able to degrade carboxymethyl cellulose. Northern (RNA) analysis showed that cel3 gene expression was induced by cellulose and repressed by glucose, fructose, 2-deoxyglucose, and lactose. Glycerol, mannitol, sorbitol, and maltose were neutral carbon sources. Nuclear run-on analysis showed that the rate of synthesis of cel3 mRNA in cellulose-grown cultures was 13 times higher than that in glucose-grown cultures. A low basal rate of cel3 mRNA synthesis was observed in the nuclei isolated from glucose-grown mycelia.

Agaricus↗
PubMed1994

A volume-dependent apneic threshold during NREM sleep in the dog.

We determined the causes of central apnea that commonly follow the hyperpnea resulting from brief airway occlusion during non-rapid-eye-movement (NREM) sleep. Ventilation and end-tidal gases were measured before, during, and after 214 trials of 15-20 s of tracheal occlusion in three dogs during NREM sleep. Airway occlusion was accompanied by progressive increases in inspiratory effort and was followed by transient one- to four-breath hyperapneas, with subsequent central apnea [3-15 times eupneic control expiratory duration (TE)] in 62% of occlusion trials. Significant TE prolongation after hyperventilation did not occur until tidal volume (VT) was three times greater than control; i.e., there was a volume-dependent apneic threshold. Transient electroencephalogram arousal at the end of the occlusion often augmented VT, thereby contributing to the subsequent central apnea; however, arousal was not required for the apnea to occur. Significant transient hypocapnia (up to -12 Torr arterial PCO2) commonly occurred after release of airway occlusion but was not closely correlated with the length of central apnea. During vagal blockade, after release of airway occlusion, significant transient hyperventilation occurred but at VT < 40% greater than control, and TE prolongation was markedly reduced. In summary, after release of airway occlusion in NREM sleep, 1) VT greater than three times eupnea was necessary to cause central apnea, 2) transient arousal at the termination of airway occlusion caused longer apneas by augmenting VT, and 3) transient hypocapnia per se made a significant but minor contribution to the postocclusion central apnea.

Airway Obstruction↗
PubMed1993

Saccharomyces cerevisiae cytoplasmic tyrosyl-tRNA synthetase gene. Isolation by complementation of a mutant Escherichia coli suppressor tRNA defective in aminoacylation and sequence analysis.

Exploiting differences in tRNA recognition between prokaryotic and eukaryotic tyrosyl-tRNA synthetases (TyrRSs), we have isolated the gene for the cytoplasmic TyrRS of Saccharomyces cerevisiae by functional complementation in Escherichia coli of a mutant E. coli tRNA. The tRNA, derived from the E. coli initiator tRNA with changes to allow suppression of amber termination codons, is poorly aminoacylated in E. coli and hence, is only a weak amber suppressor. The same tRNA functions as a good suppressor in S. cerevisiae and is aminoacylated with tyrosine by yeast extracts. We expressed a yeast cDNA library in an E. coli strain carrying the mutant tRNA gene and several genes with amber mutations. cDNA clones were isolated which increased suppression and levels of aminoacylation of the mutant tRNA. Characterization of the gene identified a methionine-initiated open reading frame encoding a protein of 394 amino acids. Expression of this protein in E. coli demonstrated that tyrosine was incorporated during suppression and that yeast cytoplasmic TyrRS activity was produced. Yeast cytoplasmic TyrRS has sequences typical of class I aminoacyl-tRNA synthetases, but only weak overall sequence similarity to the corresponding eubacterial and mitochondrial TyrRSs. However, many of the residues known to line the tyrosyl-adenylate-binding pocket of the Bacillus stearothermophilus enzyme can be aligned in the yeast sequence. These include the aspartic acid and tyrosine residues thought to contact the tyrosine side chain to provide substrate specificity.

Amino Acid Sequence↗
PubMed1993

Developmental regulation of the gene for formate dehydrogenase in Neurospora crassa.

We have isolated and characterized a gene, fdh, from Neurospora crassa which is developmentally regulated and which produces formate dehydrogenase activity when expressed in Escherichia coli. The gene is closely linked (less than 0.6 kb apart) to the leu-5 gene encoding mitochondrial leucyl-tRNA synthetase; the two genes are transcribed convergently from opposite strands. The expression patterns of these genes differ: fdh mRNA is found only during conidiation and early germination and is not detectable during mycelial growth, while leu-5 mRNA appears during germination and mycelial growth. The structure of the fdh gene was determined from the sequence of cDNA and genomic DNA clones and from mRNA mapping studies. The gene encodes a 375-amino-acid-long protein with sequence similarity to NAD-dependent dehydrogenases of the E. coli 3-phosphoglycerate dehydrogenase (serA gene product) subfamily. In particular, there is striking sequence similarity (52% identity) to formate dehydrogenase from Pseudomonas sp. strain 101. All of the residues thought to interact with NAD in the crystal structure of the Pseudomonas enzyme are conserved in the N. crassa enzyme. We have further shown that expression of the N. crassa gene in E. coli leads to the production of formate dehydrogenase activity, indicating that the N. crassa gene specifies a functional polypeptide.

Amino Acid Sequence↗