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Biomedical subjects

C S Chu

Publications and source records attributed to C S Chu.

At least 55 records · Page 3Linked to original sources

Expression of the cystic fibrosis transmembrane conductance regulator gene in cells of non-epithelial origin.

Consistent with the fact that the clinical disorder cystic fibrosis (CF) is manifested on epithelial surfaces, active transcription of the CF transmembrane conductance regulator (CFTR) gene and CFTR mRNA transcripts are detectable in a variety of epithelial cells, suggesting CFTR gene expression might be epithelial cell-specific. However, analysis of the CFTR gene promoter suggests it is a housekeeping gene, implying more widespread expression than only in epithelial cells. To evaluate the latter hypothesis, various human cells of non-epithelial origin, including lung fibroblasts, U-937 histiocytic lymphoma cells, K-562 erythroleukemia cells, HL-60 promyelocytic leukemia cells as well as freshly isolated blood lymphocytes, neutrophils, monocytes, and alveolar macrophages were examined for CFTR gene expression. Although Northern analysis failed to show CFTR mRNA transcripts in these cells, amplification of mRNA (after conversion to cDNA) by polymerase chain reaction combined with Southern analysis demonstrated the presence of CFTR mRNA transcripts at low levels in all cells evaluated except HL-60 cells. Comparative quantitative analysis showed fibroblasts contained 200-400 fold less CFTR mRNA transcripts than the T84 and HT-29 colon carcinoma epithelial cell lines, but had similar levels of CFTR transcripts to those of other epithelial cell lines. Nuclear transcription run-on analyses demonstrated very low level CFTR gene transcription in fibroblasts and U-937 cells, similar to that of other epithelial cells, but lower than the T84 and HT-29 colon carcinoma cell lines. Interestingly, while chromatin DNA of fibroblasts had no DNase I hypersensitivity sites in the 5' flanking region of the CFTR gene, HT-29 chromatin DNA exhibited four DNase I accessible sites in the same region, suggesting that these sites may be related to more active transcription of the CFTR gene in the intestinal epithelial cells than in fibroblasts.

Base Sequence↗

Expression of the cystic fibrosis transmembrane conductance regulator gene in the respiratory tract of normal individuals and individuals with cystic fibrosis.

The most common mutation of the cystic fibrosis transmembrane conductance regulator gene, CFTR, associated with the clinical disorder cystic fibrosis (CF) is called "delta Phe508," a triple-base deletion resulting in loss of phenylalanine at residue 508 of the predicted 1480-amino acid CFTR protein. In the context that the lung is the major site of morbidity and mortality in CF, we evaluated airway epithelial cells for CFTR mRNA transcripts in normal individuals, normal-delta Phe508 heterozygotes, and delta Phe508 homozygotes to determine if the normal and delta Phe508 CFTR alleles are expressed in the respiratory epithelium, to what extent they are expressed, and whether there are relative differences in the expression of the normal and abnormal alleles at the mRNA level. Respiratory tract epithelial cells recovered by fiberoptic bronchoscopy with a cytology brush demonstrated CFTR mRNA transcripts with sequences appropriately reflecting the normal and delta Phe508 CFTR alleles of the various study groups. CFTR gene expression quantified by limited polymerase chain reaction amplification showed that in normal individuals, CFTR mRNA transcripts are expressed in nasal, tracheal, and bronchial epithelial cells at approximately 1-2 copies per cell, more than 100-fold greater than in pharyngeal epithelium. Importantly, allele-specific hybridization studies demonstrated that the normal and delta Phe508 CFTR alleles are expressed in the respiratory epithelium in similar amounts.

Base Sequence↗

Down-regulation of cystic fibrosis gene mRNA transcript levels and induction of the cystic fibrosis chloride secretory phenotype in epithelial cells by phorbol ester.

To evaluate the hypothesis that phorbol myristate acetate (PMA) might modulate the expression of the cystic fibrosis (CF) gene in epithelial cells, we examined the effect of PMA on CF mRNA levels and regulation of Cl- secretion. Strikingly, PMA down-regulated CF mRNA transcript numbers in a dose- and time-dependent manner. Importantly, in parallel with the reduction of CF mRNA levels, PMA-treated cells were unable to up-regulate Cl- secretion in a normal fashion in response to forskolin, an effect which was also dose- and time-dependent. Thus, PMA is capable of modulating expression of the CF gene and induces T84 cells to adopt the "CF phenotype" in regard to regulation of Cl- ion transport.

Blotting, Northern↗

Variable deletion of exon 9 coding sequences in cystic fibrosis transmembrane conductance regulator gene mRNA transcripts in normal bronchial epithelium.

The predicted protein domains coded by exons 9-12 and 19-23 of the 27 exon cystic fibrosis transmembrane conductance regulator (CFTR) gene contain two putative nucleotide-binding fold regions. Analysis of CFTR mRNA transcripts in freshly isolated bronchial epithelium from 12 normal adult individuals demonstrated that all had some CFTR mRNA transcripts with exon 9 completely deleted (exon 9- mRNA transcripts). In most (9 of 12), the exon 9- transcripts represented less than or equal to 25% of the total CFTR transcripts. However, in three individuals, the exon 9- transcripts were more abundant, comprising 39, 62 and 66% of all CFTR transcripts. Re-evaluation of the same individuals 2-4 months later showed the same proportions of exon 9- transcripts. Of the 24 CFTR alleles in the 12 individuals, the sequences of the exon-intron junctions relevant to exon 9 deletion (exon 8-intron 8, intron 8-exon 9, exon 9-intron 9, and intron 9-exon 10) were identical except for the intron 8-exon 9 region sequences. Several individuals had varying lengths of a TG repeat in the region between splice branch and splice acceptor consensus sites. Interestingly, one allele in each of the two individuals with 62 and 66% exon 9- transcripts had a TT deletion in the splice acceptor site for exon 9. These observations suggest either the unlikely possibility that sequences in exon 9 are not critical for the functioning of the CFTR or that only a minority of the CFTR mRNA transcripts need to contain exon 9 sequences to produce sufficient amounts of a normal CFTR to maintain a normal clinical phenotype.

Base Sequence↗

Transdermal delivery of the alpha 2-agonist clonidine does not alter airways responses to inhaled histamine or methacholine.

Previous studies have reported that the inhalation of the alpha 2-agonist clonidine decreases airways reactivity. Other studies have shown that oral doses of clonidine acutely increase airways reactivity to histamine, but not to methacholine. Recently, a transdermal clonidine delivery system (TTS) has been approved for use, and there is an increasing interest in using this system for management of postmenopausal and smoking cessation symptoms. To our knowledge, the effects of TTS on airways function in asthmatics have not been reported. The purpose of this study was to determine if use of TTS would alter airways reactivity. Six asymptomatic asthmatic subjects underwent a baseline methacholine challenge (M). In a double-blinded randomized crossover fashion, either a placebo or a TTS patch (TTS-1, 0.1 mg/day), was applied to the arm. Four days later, the challenge was repeated. After two to three days of washout, the alternate patch was applied, and a second challenge was performed. Several days later, a second baseline challenge was repeated. This sequence was then repeated using histamine (H). The patch was well tolerated by all subjects. There was no significant change in resting pulse or blood pressure, and for the group no change in airways reactivity to either M or H was noted. In conclusion, while use of TTS-1 does not improve airways function, its short-term use in asthmatics is not associated with an increase in airways reactivity.

Administration, Cutaneous↗

Multiple graft harvestings from deep partial-thickness scald wounds healed under the influence of weak direct current.

The time required for wound healing, contraction, and hypertrophic scarring often limit the use of deep partial-thickness burn wounds as donor sites for split-thickness grafts. We have examined the effects of weak direct current and silver nylon dressings on the healing of partial-thickness scald burns, split-thickness grafts taken from these wounds when healed, and the resulting donor sites in a guinea pig model. Dorsal scald wounds treated with weak direct current reepithealized by 12 days postinjury. Split-thickness grafts taken from healed scald wounds showed more rapid revascularization with direct current treatment than did control grafts. Grafts and donor sites treated with direct current showed more rapid reepithelialization, decreased contraction, improved hair survival, and decreased dermal fibrosis when compared to controls not treated with direct current. Only donor wounds treated with weak direct current were reusable as donor sites.

Animals↗

Corticosteroid treatment of hemolytic anemia associated with Mycoplasma pneumoniae pneumonia.

We have described a 35-year-old man with M pneumoniae pneumonia who had severe hemolytic anemia that appeared to respond well to high-dose corticosteroid therapy. Whether corticosteroids have value in decreasing the severity of hemolytic anemia due to cold agglutinin and other protean extrapulmonary manifestations with M pneumoniae infection needs further controlled study. Our experience suggests that corticosteroids may be beneficial.

Adult↗

Therapeutic effects of silver nylon dressings with weak direct current on Pseudomonas aeruginosa-infected burn wounds.

The therapeutic and prophylactic effects of nylon dressings coated with metallic silver in a direct current circuit have been examined in a rat model of fatal burn wound sepsis. Male Sprague-Dawley rats weighing 325 +/- 25 grams with 20% full-thickness scald injuries were used. Therapeutic effects were examined at 4 or 24 hours after surface inoculation with a lethal dose of Pseudomonas aeruginosa (Strain 59-1244). When used as a surface anode with an implanted silver needle cathode, the silver nylon was therapeutic at currents between 0.4 and 40 microA when applied at either test time and continued for 5 days (p less than 0.001). When used as a cathode, silver nylon was not effective. Nylon cloth without a silver metal coating was not effective without applied current or when used as an anode. Silver nylon dressings placed at 4 hours after inoculation but without applied current showed significant effectiveness (p less than 0.01). This effect, however, was significantly less than that seen with silver nylon used as an anode (p less than 0.001). Barrier prophylactic effects were examined by placing silver nylon or uncoated nylon on burn wounds before inoculation with Pseudomonas aeruginosa. The uncoated nylon had no barrier effect. Silver nylon was found protective but applied current was not required for significant (p less than 0.001) barrier effect. These results indicate silver nylon dressings may be a valuable antimicrobial burn wound covering device.

Animals↗

Spontaneous perforation of the common hepatic duct: report of seven cases.

Spontaneous perforation of the common hepatic duct is rare. Only 11 cases have been reported since McWilliams reported the first in 1912. Herewith, seven patients with spontaneous perforation of the hepatic duct treated between 1953-1980 at the Hunan Medical College Hospital in Ghangsha, China are added.

Adolescent↗

Cholelithiasis in children in a Chinese hospital: report of 52 cases.

Over a period of 22 years (1958-1980), 52 children with cholelithiasis were treated in the Hunan Medical College Hospital in Ghangsha, China. Enteric helminthiasis is a common endemic disease in China and the countries of the Far East. Common in this region also is biliary ascariasis, which can precipitate an abdominal emergency in children. Both these conditions make differentiation of primary acute cholecystitis from the acute cholecystitis that is a complication of biliary ascariasis difficult in children. But, whatever the etiology of the disease, cholelithiasis was confirmed in all 52 children, an incidence of 1:62.4 the frequency of this disease in adults, or eight times higher than that which occurs in Western countries. Table 1 shows the distribution according to sex and age in our patients.

Adolescent↗

Chemical pulmonary burn injury and chemical intoxication.

Two large groups of patients with chemical pulmonary burns who sustained their injuries in the same environment were presented. Data from the blaze smoke analysis of two imitative experiments which were performed under the same conditions as were present when these patients sustained their burns showed a high concentration of carbon monoxide of 35700-571400 ppm and multivariable components of chemicals. The environmental conditions, the clinical course, laboratory findings and blaze analysis clearly demonstrated the close relationship between chemical pulmonary burn injury and chemical intoxication which increased the difficulty in treatment. Ideally, the initial treatment at the site of the fire is the application of 100 per cent oxygen in high flow by mask, and temporary artificial hyperventilation after hospitalization will give a satisfactory result if the fire victim suffers severe carbon monoxide poisoning. In order to treat chemical intoxication in the patient with chemical pulmonary burns successfully, we have adopted a regimen of 'over-loading fluid resuscitation', together with diuretics and positive end expiratory pressure (PEEP) under the monitoring of central venous pressure.

Burns, Chemical↗

Burns updated in China: I. Cutaneous thermal burns.

Clinical research on burns has developed substantially in China since 1958. Having the rich inheritance of our traditional medicine the study of burn treatment in our country has developed in a way somewhat different from that in Western countries. In this paper, the outcome of the clinical practice and research work related to traditional herbal medicine in fluid resuscitation and wound management is briefly described. In the field of estimation of the surface area and depth classification, immunology and its clinical practice of skin graft, burn wound sapremia and burn septicemia, much clinical and laboratory research work was studied by the Chinese surgeons in the past 10 years. Also, prevention of scar overgrowth and deformity following its burn contracture by prophylactic management is discussed.

Adult↗

Burns updated in China: II. Special burn injury and burns of special areas.

The pathogenesis, pathology, classification, clinical features and prognosis of pulmonary burn injury have been studied recently by Chinese surgeons. New methods to treat electrical contact burns and chemical burns are introduced in this paper. The initial attempt to use microvascular surgical technic for repairing the post-burned tissue defect has developed successfully in China.

Burns↗

New concepts of pulmonary burn injury.

Based on our experience with two large groups of fire victims injured in a semiclosed environment, the clinical course of the survivors, and the pathologic examination of those who died, a modified classification of pulmonary burns into thermal burns and chemical burns is suggested. The results of our study indicate a close relationship between carbon monoxide poisoning and chemical intoxication in patients injured in a relatively closed environment. The clinical course and prognosis of patients suffering from a thermal pulmonary burn are different from that of a chemical pulmonary burn.

Burns, Inhalation↗