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Biomedical subjects

C L Wu

Publications and source records attributed to C L Wu.

At least 55 records · Page 3Linked to original sources

Indolent cutaneous mucormycosis with pulmonary dissemination in an asthmatic patient: survival after local debridement and amphotericin B therapy.

We describe a 68-year-old asthmatic female patient with multiple pulmonary cavities. A preexisting ecthyma on the left lower leg became erythematous and swollen during exacerbation of her asthma which was under treatment with high-dose steroids. Nonseptate broad hyphae were found in her sputum, pus from the wound, and debrided skin tissue. Hematogenous spread of septic emboli from indolent cutaneous mucormycosis to both lungs was the suspected mechanism of dissemination. High-dose steroid therapy may have been the major contributory factor. The patient was successfully treated with local surgical debridement of the wound and intravenous amphotericin B.

Aged↗

Novel cystic fibrosis mutation (2215insG) in two adolescent Taiwanese siblings.

Cystic fibrosis (CF) is an autosomal recessive disorder that is rarely found in Asians. Only four cases of CF from four different families have been reported in Taiwan. We report two cases of CF involving two teenage siblings. Both presented with repeated airway infections, poor weight gain, clubbing of the fingers, hypoxemia, and obstructive ventilatory impairment. Multiple focal bronchiectases and emphysema were demonstrated on high-resolution computed tomography. Sweat chloride concentrations, as measured using the modified sweat chloride test in a closed space with a heater, were 327 mmol/L and 276 mmol/L, respectively. To confirm the CF diagnosis, DNA mutation analysis was performed. All 27 exons of the CF transmembrane conductance regulator (TR) gene and their flanking intron sequences were screened for nucleotide sequence alterations, and the mutations were then identified by direct DNA sequence analysis. Both siblings carried 1898 + 5G-->T; a mutation previously identified in Taiwan. In addition, the mutation analysis identified a new single-base-insertion mutation in exon 13 on the second CFTR allele of these patients. This mutation, named 2215insG, is expected to cause a significant disruption of CFTR function. The 1898 + 5G-->T/2215insG genotype is thus consistent with the CF diagnosis. A new missense mutation, S895N, in exon 15 of the CFTR gene, which cosegregated with 2215insG, was also identified in both of these patients.

Adolescent↗

Postoperative analgesic requirements in patients undergoing arthroscopic anterior cruciate ligament reconstruction.

Anterior cruciate ligament (ACL) procedures are associated with significant postoperative pain and have traditionally been done on a short-stay hospitalization basis because of concerns for adequate postoperative analgesia. A retrospective chart review was performed to determine postoperative intravenous patient-controlled analgesia (PCA) morphine requirements for 80 patients who had undergone arthroscopically assisted ACL reconstruction under general anesthesia by means of a patellar tendon autograft by 1 of 2 surgeons. The mean +/- SD PCA morphine used after surgery was 20.4+/-20.0 mg. There was a wide interpatient difference in postoperative opioid consumption: the amount of PCA morphine used ranged from 0 mg to 124 mg. A comparison between the surgeons revealed that 1 surgeon had significantly longer intraoperative surgical, tourniquet, and anesthesia times; however, there was no difference in the length of recovery room stay, amount of postoperative PCA morphine used, or time to hospital discharge. Predicting which patients may benefit from short-stay hospitalization after arthroscopic ACL reconstruction may be difficult because of considerable interpatient differences in postoperative analgesic requirements.

Adult↗

[The studies on protective effects of SM against myocardial hypoxia/reoxygenation injury].

AIM AND METHODS: To assess the myocardial effects of Salvia Miltiorrhiza (SM) injection against hypoxia-reoxygenation injury, 31P NMR was used to trace the time courses of high energy phosphates (HEP) content and intracellular pH (pHi) of the isolated perfused rat hearts under hypoxia (30 min) and subsequent reoxygenation (40 min). RESULTS: It was discovered that SM significantly preven-ted the decrease in the myocardial HEP content during hypoxia, enhanced the recovery of myocardial phosphocreatine (PCr), adenosine triphosphate (ATP) and the PCr/Pi (inorganic phosphate) ratios during reoxygenation, and lightened the decrease of the myocardial pHi value caused by hypoxia. CONCLUSION: SM improves the myocardial energy metabolism level during prolonged hypoxia and subsequent reoxygenation and protects myocardium against hypoxia/reoxygenation injury. SM significantly attenuates acidosis during hypoxia and prevents the appearance of very acidic areas of the myocardium after reoxygenation.

Animals↗

Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis.

Papillon-Lefèvre syndrome, or keratosis palmoplantaris with periodontopathia (PLS, MIM 245000), is an autosomal recessive disorder that is mainly ascertained by dentists because of the severe periodontitis that afflicts patients. Both the deciduous and permanent dentitions are affected, resulting in premature tooth loss. Palmoplantar keratosis, varying from mild psoriasiform scaly skin to overt hyperkeratosis, typically develops within the first three years of life. Keratosis also affects other sites such as elbows and knees. Most PLS patients display both periodontitis and hyperkeratosis. Some patients have only palmoplantar keratosis or periodontitis, and in rare individuals the periodontitis is mild and of late onset. The PLS locus has been mapped to chromosome 11q14-q21 (refs 7, 8, 9). Using homozygosity mapping in eight small consanguineous families, we have narrowed the candidate region to a 1.2-cM interval between D11S4082 and D11S931. The gene (CTSC) encoding the lysosomal protease cathepsin C (or dipeptidyl aminopeptidase I) lies within this interval. We defined the genomic structure of CTSC and found mutations in all eight families. In two of these families we used a functional assay to demonstrate an almost total loss of cathepsin C activity in PLS patients and reduced activity in obligate carriers.

Aggressive Periodontitis↗

Neopallavicinin from the Taiwanese liverwort Pallavicinia subciliata.

Neopallavicinin (2), a diastereomer of pallavicinin (1), was identified from the Taiwanese liverwort Pallavicinia subciliata. The structure of neopallavicinin was deduced by spectroscopic analysis. Three chemotypes may be classified for the species Pallavicinia subciliata.

Diterpenes↗

Meta-PCR: a novel method for creating chimeric DNA molecules and increasing the productivity of mutation scanning techniques.

Many mutation scanning techniques are capable of locating mutations in DNA fragments much larger than the average exon. We have developed a system called Meta-PCR that can maximize the length of sequence scanned by these techniques, improving their productivity and realizing their full potential. Meta-PCR is a simple, versatile, and powerful method for generating chimeric DNA molecules. Currently, up to five PCR amplifiable fragments can be combined to form a single linear amplimer. The Meta-PCR reaction is self-assembling and takes place in two coupled stages carried out in a single reaction vessel. The order of fragments is reproducible and determined by primer design. We have developed two Meta-PCR assays, one comprising exons 6-10 of the Neurofibromatosis type 2 (NF2) gene and the second exons 8-12 of the human mismatch repair gene, hMLH1. We verified by direct sequencing that the order and sequence of the component exons in the Meta-PCR products is as predicted. Meta-PCR products from seven previously ascertained heterozygotes for NF2 mutations were directly sequenced. All seven mutations were clearly visible as mixed bases at the expected nucleotide, confirming that Meta-PCR faithfully reproduces the original sample genotype. We have evaluated the downstream use of the NF2 Meta-PCR products in fluorescent solid-phase chemical cleavage of mismatches (CCM). Meta-PCR products from eleven NF2 mutant heterozygotes were screened retrospectively for piperidine cleavage after hydroxylamine or potassium permanganate modification of mismatched bases. Ten of the 11 mutants were detected by visible cleavage. One mutation predicted to be cleaved after potassium permanganate modification was not detected. However, we were able to attribute this false negative to a failure in the CCM method. Meta-PCR is likely to be useful to clinical molecular diagnostic laboratories, helping them to fulfill demand for rapid and accurate screening for point mutations in large multi-exon genes.

Adaptor Proteins, Signal Transducing↗

Sinonasal lymphoma: a clinicopathologic analysis of 58 cases from the Massachusetts General Hospital.

Few large series compare lymphomas of the nasal cavity with those of the paranasal sinuses. We studied the cases of 58 patients, 34 males and 24 females, aged 7 to 92 years (mean, 57 years), who had lymphoma involving the nasal cavity or paranasal sinuses. Thirty-three patients had diffuse large B-cell lymphoma (DLBCL). Twenty-three were male and 10 were female, with an age range of 7 to 91 years (mean, 63 years); two were HIV-positive. Only 2 of 11 cases tested (one in an HIV-positive patient and one of lymphomatoid granulomatosis type) were Epstein-Barr virus (EBV)-positive. Thirty (91%) involved paranasal sinuses, 10 with nasal involvement, whereas three cases had nasal, but not sinus, involvement. At last follow-up, 16 (67%) were free of disease 7 to 169 months later (mean, 65 months), and 8 (33%) had died of disease 2 to 166 months later (mean, 45 months). Seventeen patients had nasal-type natural killer (NK)/T-cell lymphoma. There were 10 women and 7 men, aged 27 to 78 years (mean, 48 years). Thirteen of 14 were EBV-positive. Sixteen patients had nasal involvement, eight with sinus involvement. Eleven (73%) of 15 were alive and well 6 to 321 months later (mean, 139 months), three (20%) died of lymphoma 1, 11, and 12 months later, and one (7%) is alive with disease. There was one case each of marginal zone B-cell lymphoma, Burkitt's lymphoma, Burkitt-like lymphoma, peripheral T-cell lymphoma of unspecified type, and adult T-cell lymphoma/leukemia. In an additional three cases, the lymphomas were composed predominantly of large cells, but no immunophenotyping could be performed for subclassification. In 19 cases (17 DLBCLs, 1 Burkitt-like lymphoma, and 1 lymphoma of uncertain lineage), presenting symptoms included complaints related to the eyes. In 16 cases (13 DLBCLs, 1 Burkitt-like lymphoma, 1 nasal NK/T-cell lymphoma, and 1 lymphoma of uncertain lineage), the orbit was invaded by lymphoma. In our series, the most common lymphoma to arise in the sinonasal area is DLBCL, followed by nasal NK/T-cell lymphoma. Comparison of these two types of lymphoma showed that lymphomas involving sinuses without nasal involvement were predominantly DLBCLs (20 of 21), whereas nasal cavity lymphomas without sinus involvement were usually NK/T-cell type (8 of 11) (p = 0.000125). Compared with patients with DLBCL, patients with nasal NK/T-cell lymphoma were overall younger, with a lower male-to-female ratio. Lymphomas of B-cell lineage were more likely to be associated with symptoms related to the eyes (p < 0.0005) and to have extension to the orbit (p < 0.01) than were lymphomas of T- or NK-cell lineage. In contrast to results of Asian studies in which nasal NK/T-cell lymphoma has a very poor prognosis, our nasal NK/T-cell lymphomas had an outcome similar to that of DLBCL.

Adolescent↗

Thoracic epidural analgesia versus intravenous patient-controlled analgesia for the treatment of rib fracture pain after motor vehicle crash.

BACKGROUND: Pain from rib fracture pain may affect pulmonary function, morbidity, and length of intensive care unit stay. Previous trials have varied epidural technique within the study and have used several outcome variables. METHODS: The charts of patients who sustained rib fractures after a motor vehicle crash between January 1, 1994, and June 30, 1997, were reviewed. Data were collected from 64 patients who had three or more rib fractures and initiation of intravenous patient-controlled analgesia with morphine or thoracic epidural analgesia with bupivacaine and fentanyl within 24 hours of admission. RESULTS: Injury Severity Score and Acute Physiology and Chronic Health Evaluation II scores were not significantly different between groups. Patients in the epidural group had significantly more rib fractures and were significantly older. Patients who received epidural analgesia had significantly lower pain scores at all times. There were no differences in the lengths of intensive care unit or hospital stays, or the incidence of pulmonary complications or organ failure between groups. CONCLUSION: Thoracic epidural analgesia with bupivacaine and fentanyl provided superior analgesia than intravenous patient-controlled analgesia morphine.

APACHE↗

Using 99mTc-DTPA radioaerosol inhalation lung scintigraphies to detect the lung injury induced by consuming Sauropus androgynus vegetable and comparison with conventional pulmonary function tests.

Consuming Sauropus androgynus, a Malaysian plant, to reduce body weight began to become fashionable in Taiwan in 1994. According to some reports, people consuming this vegetable developed lung injuries. From July to November 1995, there were 81 nonsmoking women admitted to our hospital. Thirty-six cases had respiratory symptoms/signs and the remaining 45 had no symptoms/signs. We investigated these patients with pulmonary function tests (PFT) and technetium-99m DTPA radioaerosol inhalation lung scintigraphies (DTPA lung scan), a test to evaluate the lung ventilation and alveolar epithelial permeability. Eighteen patients had abnormal results in PFT, including obstructive type (n = 17), restrictive type (n = 5), and both (n = 4). There were 33 patients with abnormalities in DTPA lung scans, including unhomogeneous deposition of DTPA radioaerosols (n = 19), faster clearance of radioaerosols from lung (n = 26), and both (n = 12). Analyzing the results, we found that the patients with respiratory symptoms had a higher incidence of abnormal results of PFT and DTPA lung scans than the patients without respiratory symptoms (p < 0.05). Besides, we found that the DTPA lung scan was more sensitive than chest x-ray and PFT in detecting the lung injuries related to the consumption of S. androgynus (p < 0.05). Consuming S. androgynus can result in symptomatic or asymptomatic lung injuries, manifested as obstructive or restrictive ventilatory impairment, unhomogeneous radioaerosol distribution, and increased alveolar epithelial permeability. In addition, measurement of the 99mTc-DTPA clearance is the most sensitive test to detect the lung injuries caused by consuming S. androgynus.

Adolescent↗

DNA studies underestimate the major role of CDKN2A inactivation in oral and oropharyngeal squamous cell carcinomas.

Loss of CDKN2A expression was demonstrated by immunohistochemistry in 87% of oral and oropharyngeal squamous cell carcinoma (OSCC) primary tumor samples. By contrast, DNA studies showed a much lower frequency of loss of the CDKN2A gene. Point mutations and promoter methylation of CDKN2A were seen in 7% and 23%, respectively, of primary tumors. Loss of heterozygosity analysis using a dense set of 9p markers showed allelic imbalance that included CDKN2A in only 31% of samples, but a further 47% showed loss at loci near CDKN2A with apparent retention of CDKN2A. No tumor with any allelic imbalance expressed CDKN2A, whether or not the imbalance appeared to involve the CDKN2A locus. We interpret these data as showing partially overlapping deletions on the two 9p homologues, with homozygous deletion of CDKN2A masked by amplification of contaminating stromal material. Our data show that inactivation of the CDKN2A gene products is a near-universal step in the development of oral and oropharyngeal squamous cell carcinomas, and we suggest that homozygous deletion is the most common mechanism of inactivation. The CDKN2A locus may be particularly prone to deletion because it encodes two unrelated tumor suppressor proteins, CDKN2A (p16INK4a) and p19ARF, and deletion, but not point mutation or methylation, would inactivate both gene products. However, our results also suggest that complex patterns of allelic imbalance in primary squamous carcinomas in general may not provide reliable evidence for the existence of multiple tumor suppressor genes within a single chromosomal region.

5' Untranslated Regions↗

Hepatitis C virus core protein fused to hepatitis B virus core antigen for serological diagnosis of both hepatitis C and hepatitis B infections by ELISA.

The sequence encoding the truncated core protein (amino acids 1-98) of hepatitis C virus (HCc) was expressed in E. coli for production of HCc(1-98), or fused with the truncated core antigen (HBcAg) and segments from the preS1 and preS2 regions from hepatitis B virus (HBV) for production of HBcPreS1PreS2HCc(1-98). The HCc(1-98) and HBcPreS1PreS2HCc(1-98) proteins reacted with sera from HCV-infected individuals by immunoblot analyses, while the latter protein also exhibited HBV core antigenicity. They induced antibodies against HBcAg and/or HCV core protein in rabbits and in mice. Moreover, HBcPreS1PreS2HCc(1-98) is more immunogenic than HCc(1-98) in terms of anti-HCc induction. An ELISA that employed recombinant HCV core antigens of either HCc(1-98) or HBcPreS1PreS2HCc(1-98) to detect anti-HCc and/or anti-HBc antibodies was developed. Evaluation of serum samples with different status of HBV and HCV infections suggested that HCc(1-98) might be suitable for the determination of antibodies against HCV core protein, while HBcPreS1PreS2HCc(1-98) might be of value to detect HCV and/or HBV infection in donated blood in HBV low-prevalence countries.

Animals↗

Two-dimensional crystallization and projection structure of KcsA potassium channel.

Potassium channels are integral membrane proteins that play a crucial role in regulating diverse cell functions in both electrically excitable and non-excitable cells. Molecular cloning has revealed a diverse family of genes that encode these proteins, and a variety of experimental strategies have defined functional domains. We have cloned, over-expressed and purified the KcsA potassium channel to homogeneity and reconstituted this channel protein with phospholipids to form two-dimensional crystals. The crystals belong to plane group p4 and have unit cell dimensions of a=b=48 A. A projection map at 6 A resolution has been obtained by electron crystallography. The map shows that the protein is a homotetramer, having a low-density region on the 4-fold axis that is the site of the ion conduction pathway. Each monomer contains density features that are consistent with the molecular model of a truncated form of KcsA recently determined by X-ray crystallography.

Bacterial Proteins↗

Clinical and electrophysiologic attributes as predictors of results of autonomic function tests.

Autonomic dysfunction is a feature of some neuropathies and not others. It has been suggested that some clinical and electrophysiologic attributes are predictable of autonomic impairment detected using laboratory testing; however, dear guidelines are unavailable. We evaluated 138 relatively unselected patients with peripheral neuropathy who underwent neurologic evaluation, electromyography (EMG), nerve conduction studies, and autonomic function tests to determine which variables were predictive of laboratory findings of autonomic failure. The variables evaluated were 1) clinical somatic neuropathic findings, 2) clinical autonomic symptoms, and 3) electrophysiologic findings. Autonomic symptoms were strongly predictive (Rs = 0.40, p < 0.001) of autonomic failure. Among the non-autonomic indices, absent ankle reflexes were mildly predictive (Rs = 0.19, p = 0.022) of autonomic impairment, but all others were not (duration, clinical pattern, severity, weakness, sensory loss). Electrophysiologic changes of an axonal neuropathy predicted autonomic impairment while demyelinating neuropathy did not. We conclude that autonomic studies will most likely be abnormal in patients who have symptoms of autonomic involvement and those who have an axonal neuropathy.

Autonomic Nervous System Diseases↗

Provision of positive and negative selections in retroviral vectors containing the cytosine deaminase gene.

The E. coli cytosine deaminase (CD) provides a negative selection system for suicide gene therapy as CD transfectants are eliminated following 5-fluorocytosine (5FC) treatment. Here we report a positive selection system for the CD gene using 5-fluorouracil (5FU) and cytosine in selection medium to screen for CD-positive transfectants. It is based on the relief of 5FU toxicity by uracil which is converted from cytosine via CD catalysis, as uracil competes with the toxic 5FU in subsequent pyrimidine metabolism. Hence, a retroviral vector containing the CD gene may provide both positive and negative selections after gene transfer. The CD transfectants selected with the positive selection system showed susceptibility to 5FC in subsequent negative selection in vitro and in vivo. Therefore, this dual selection system is useful not only for combination therapy with transgene and CD gene, but can also act to eliminate selectively transduced cells after the transgene has furnished its effects or upon undesired conditions if 5FC is applied for negative selection in vivo.

Animals↗

Clinical evaluation of C7 spinal nerve transection: 21 patients with at least 2 years' follow-up.

We have performed C7 spinal nerve transfer to treat root injury of the brachial plexus since 1989. Out of a total of 43 patients, 21 have been followed up for at least 2 years. Evaluation of the effect of C7 transection included clinical examination, intraoperative C7 stimulation, LIDO Workset machine and electrophysiological studies to test C7 innervated muscles, and histochemical analysis of the anterior and posterior division of the upper trunk using acetylcholinesterase stain. Nearly half of the study group (48%) reported no significant sensory changes and most patients (81%) did not notice any weakness of the limb following C7 transection. Some patients did experience sensory and motor abnormalities which were most frequent during the first postoperative month, improved during the 2nd month and in most cases resolved in the 3rd postoperative month. The only longer persistent abnormality was the triceps reflex, which becomes weak or absent. We also found that intraoperative C7 stimulation was a useful predictor of possible post-transection morbidity. Subclinical deficits, detected by the LIDO workset machine and by electro-physiological studies, were quite common. Histochemical analysis revealed that the posterior division of C7 had more motor fibres than the anterior division.

Adolescent↗

Somatic mosaicism: a common cause of classic disease in tumor-prone syndromes? Lessons from type 2 neurofibromatosis.

Blood samples from 125 families with classic type 2 neurofibromatosis with bilateral vestibular schwannomas were analyzed for mutations in the NF2 gene. Causative mutations were identified in 52 families. In five families, the first affected individual in the family (the index case) was a mosaic for a disease-causing mutation. Only one of nine children from the three mosaic cases with children are affected. Four of these nine children inherited the allele associated with the disease-causing mutation yet did not inherit the mutation. NF2 mutations were identified in only 27/79 (34%) of sporadic cases, compared with 25/46 (54%) of familial cases (P<.05). In 48 families in which a mutation has not been identified, the index cases have had 125 children, of whom only 29 are affected with NF2 and of whom only a further 21 cases would be predicted to be affected by use of life curves. The 50/125 (40%) of cases is significantly less than the 50% expected eventually to develop NF2 (P<.05). Somatic mosaicism is likely to be a common cause of classic NF2 and may well account for a low detection rate for mutations in sporadic cases. Degrees of gonosomal mosaicism mean that recurrence risks may well be <50% in the index case when a mutation is not identified in lymphocyte DNA.

Adult↗