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Biomedical subjects

D Cheng

Publications and source records attributed to D Cheng.

At least 73 records · Page 4Linked to original sources

SNARE complex proteins, including the cognate pair VAMP-2 and syntaxin-4, are expressed in cultured oligodendrocytes.

Myelin membrane synthesis in the CNS by oligodendrocytes (OLs) involves directed intracellular transport and targeting of copious amounts of specialized lipids and proteins over a relatively short time span. As in other plasma membrane-directed fusion, this process is expected to use specific trafficking and vesicle fusion proteins characteristic of the SNARE model. We have investigated the developmental expression of SNARE proteins in highly enriched primary cultures of OLs at discrete stages of differentiation. VAMP-2/synaptobrevin-2, syntaxin-2 and -4, nsec-1/munc-18-1, Rab3a, synaptophysin, and synapsin were expressed. During differentiation, expression of the vesicular SNARE VAMP-2, the small GTP-binding protein Rab3a, and the target SNARE syntaxin-4 were up-regulated. VAMP-2 and Rab3 proteins detected immunocytochemically in cultured OLs were localized within the developing process network; in situ anti-VAMP-2 antibody stained the perikarya of rows of cells with the distribution and appearance of OLs. We discuss the potential involvement of SNARE complex proteins in a plasma membrane-directed transport mechanism targeting nascent myelin vesicles to the forming myelin sheath.

Animals↗

Vascular endothelial growth factor in pleural fluid.

STUDY OBJECTIVES: The purpose of this study was to analyze the relationship of the pleural fluid vascular endothelial growth factor (VEGF) level with the diagnostic category and with the pleural fluid characteristics in a group of 70 patients. DESIGN: The VEGF levels of consecutive patients undergoing therapeutic thoracentesis were determined with an enzyme-linked immunosorbent assay. SETTING: University-affiliated tertiary care center. RESULTS: The median level of pleural fluid VEGF in the patients with congestive heart failure (150 pg/mL) was significantly (p < 0.05) lower than the median level in the patients with coronary artery bypass grafting (357 pg/mL), which in turn was significantly lower (p < 0.05) than the median levels in the patients with malignancy (1,097 pg/mL). The overlap between groups, however, limits the diagnostic usefulness of pleural fluid VEGF levels. The VEGF level was most closely correlated with the lactate dehydrogenase level (r = 0.42, p < 0.001) and was also significantly correlated with the total pleural fluid protein level. The median VEGF levels in the pleural fluid of patients with breast cancer were significantly lower (p = 0.017) than in those with lung cancer. The VEGF level was very high (3,294 pg/mL) in the one patient with pulmonary embolism. CONCLUSIONS: We conclude that the VEGF levels in pleural fluid differ significantly from one diagnostic category to another with the highest median levels occurring in patients with malignant pleural effusions. We speculate that VEGF may be responsible for the pleural fluid accumulation in at least some situations.

Breast Neoplasms↗

Mitomycin chemotherapeutic pleurodesis to palliate malignant pleural effusions secondary to gynecological cancer.

BACKGROUND: To assess the efficacy of mitomycin pleurodesis in women with end stage malignant effusion. METHODS: Retrospective analysis. RESULTS: Of the 13 patients treated six had ovarian, six had endometrial and one had cervical adenocarcinoma. The median time of onset of effusion from diagnosis of primary disease was 12 months (range 1-75). Ten patients were evaluable for response. The median age of the patients was 59 years (range 42 to 74). Ten (77%) of them had repeated thoracocentesis prior to mitomycin pleurodesis. The median duration and volume of drainage was 4 days (range 2-11) and 3.1 liters (range 1.2-10.2) respectively. One of two patients developed a pneumothorax and required the insertion of an additional chest drain. Overall, seven patients (70%) responded - one completely (CR) and six partially (PR), while three did not respond. Four of five patients with ovarian cancer had a partial response, two of four patients with endometrial cancer (one CR and one PR) responded. The only patient with cervical cancer had a partial response. Nine patients (69%) had enough symptomatic improvement to be discharged home. The drug cost of bleomycin 60 units (US$191), another commonly used agent, was more than twice as expensive as mitomycin 30 mg (US$84). CONCLUSIONS: Mitomycin pleurodesis can palliate 70% of patients for at least 1 month. It offers cheap and effective palliation. There is a suggestion that patients' quality of life is improved.

Adult↗

Wide local excision (WLE) for vaginal intraepithelial neoplasia (VAIN).

BACKGROUND: To assess the use of wide local excision in the treatment of VAIN. METHODS: A retrospective review on 40 WLE procedures for VAIN. RESULTS: The mean age was 60 years. Thirty-six (90%) patients had previous treatment for genital tract cancer or pre-cancer. The median duration and blood loss during operation was 45 minutes and 50 mls respectively. Fifteen complications affected 11 patients. Only one of five patients with 'vaginal cancer' was diagnosed prior to WLE. Of the 35 patients treated for VAIN 3, 12 (34%) developed abnormal cytology during follow up three had residual VAIN 3, five had recurrent VAIN 3 and four had invasive cancer diagnosed. The remaining 23 (66%) patients were disease free at a median follow up of 44 months. CONCLUSIONS: Ablative therapy for VAIN 3 is unsafe as occult invasive foci can be missed by biopsy. WLE is efficacious in treating high grade VAIN 3. Long term surveillance of the lower genital tract is needed to diagnose metachronous lesions.

Aged↗

Family planning training in Maryland family practice and obstetrics/gynecology residency programs.

OBJECTIVE: To examine the extent of family planning and abortion training in Maryland family practice (FP) and obstetrics/gynecology (OB) residency training programs. METHODS: All final-year residents in every FP and OB residency training program in Maryland were asked in 1998 how many cases (0, 1-10, > 10) of ten methods of contraception and abortion they had managed. RESULTS: Seventy-five percent (55) of the 73 residents responded. Fifty percent of FP residents had never inserted an intrauterine device (IUD), 43% had never inserted an implant (Nor-plant), 37% had never prescribed emergency contraceptive pills, and 30% had never fitted a diaphragm. Ninety-seven percent of FP residents had no experience with elective termination of pregnancy, and 83% had no experience with sterilization. Twenty percent of OB residents had never inserted an IUD, 16% had never inserted implants or prescribed emergency contraceptive pills, 20% had never fitted a diaphragm, and 36% had no experience in elective termination of pregnancy. Not one FP resident had inserted or fitted more than ten IUDs, implants, diaphragms, or cervical caps. Except for oral and injectable contraception, the majority of OB residents had not managed more than ten cases of any other reversible contraceptive method: 80% had not inserted more than ten IUDs, 72% had not inserted more than ten implants, 88% had not fitted more than ten diaphragms, and 100% had not fitted more than ten cervical caps. CONCLUSION: These survey results indicate a need for more formal instruction in most contraceptive methods for OB and FP residency programs in Maryland. This study concurs with previous national studies showing deficits in family planning training.

Contraceptive Devices, Female↗

[Demonstration for periodicity of leptospirosis in Yichang City of Hubei Province during 1960-1997].

OBJECTIVE: To study the periodicity of leptospirosis incidence. METHODS: Data of leptospirosis epidemics in Yichang City collected during the past 38 years from 1960 to 1997 were analyzed with periodic graphics method. RESULTS: Cause-specific incidence rate of leptospirosis was 15.43 per 100,000 in average, with an epidemic interval of 10 years, with statistical significance in periodic vibration (J = 4.179, P < 0.05). CONCLUSION: The results mentioned above provided scientific basis for the effective control and prevention of the disease.

China↗

[Endarterectomy for carotid stenosis].

OBJECTIVE: To discuss the indications, anesthesia and surgical techniques of carotid endarterectomy (CEA). METHODS: Twenty-two sides of carotid stenosis were revealed in 20 patients. CEA was performed under general anesthesia in 21 sides and local anesthesia in one. The time of carotid occlusion ranged from 27 to 52 minutes (average 35.5 min) in 20 operations, and intraoperative shunt was used in the other two. Fifteen operations were monitored with EEG. RESULTS: The postoperative course was uneventful in 17 patients after 18 operations, while transient muscle strength decrease on contralateral side and ipsilateral lower facial paresis occurred after three operations in the other three patients. Nineteen patients were followed-up for 38 months on the average. Among nine patients with TIA, ischemic attacks ceased in eight and decreased in one. Improvement was achieved in six patients with cerebral infarction. One patient without symptoms of carotid ischemia was still normal after operation. CONCLUSION: Carotid endarterectomy is a safe and effective way for treating carotid stenosis.

Adult↗

[The change of plasma level of endothelin-1 in patients with cor pulmonale and the effects of Captopril].

The purpose of this study was to investigate the role of endothelin(ET) in the development of cor pulmonale and the mechanism of captopril in treatment. The plasma ET-1 levels of 36 patients with cor pulmonale and 20 normal subjects were measured by radioimmunoassay. Twenty patients were treated with antibiotics and oxygen, and the other 16 patients were treated with antibiotics, oxygen and captopril for 14 days. The results showed that the ET-1 level of patients with cor pulmonale (88.9 +/- 8.9 ng/L) was significantly higher than that of normal control (53.5 +/- 5.1 ng/L). After treatment, the ET-1 level declined significantly in both groups of patients (P < 0.01); the ET-1 level in patients treated with captopril was lower than that in patients not treated with captopril (P < 0.05), but the level of ET-1 in patients was still higher than that of normal control (P < 0.05). These suggest that ET-1 may play an important role in the onset of cor pulmonale and captopril can reduce the ET-1 level.

Adult↗

[The diagnostic and therapeutic value of flexible bronchoscopy in foreign-body aspiration misdiagnosed as other respiratory diseases].

To explore the causes of missed diagnosis of foreign-body aspiration and summarize the experiences on the diagnostic and therapeutic use of flexible bronchoscopy (FB) in these patients. Twelve cases of foreign-body aspiration misdiagnosed as other respiratory diseases, confirmed by FB examination were analyzed. All of these patients had no histories of foreign-body aspiration, and no foreign-body shadows were found on their chest films. But there were atelectasis, hilar enlargement and obstructive pneumonia found on the films. Among the patients in this group, 7 cases were misdiagnosed as lung cancer, 2 cases of pneumonia and asthma each, and 1 case as tuberculosis. The diagnoses of all the 12 cases were confirmed by FB examinations. The foreign-bodies of the 11 cases were successfully grasped and taken out through the FB. This suggests that FB should be of great diagnostic and therapeutic value in patients with foreign-body aspiration misdiagnosed as other respiratory diseases.

Adolescent↗

Isolation of cholesterol-requiring mutant Chinese hamster ovary cells with defects in cleavage of sterol regulatory element-binding proteins at site 1.

The synthesis and uptake of cholesterol requires transcription factors designated sterol regulatory element-binding proteins (SREBPs). SREBPs are bound to membranes in a hairpin orientation with their transcriptionally active NH2-terminal segments facing the cytosol. The NH2-terminal segments are released from membranes by two-step proteolysis initiated by site 1 protease (S1P), which cleaves in the luminal loop between two membrane-spanning segments. Next, site 2 protease (S2P) releases the NH2-terminal fragment of SREBP. The S2P gene was recently isolated by complementation cloning using Chinese hamster ovary cells that require cholesterol for growth, due to a mutation in the S2P gene. A similar approach cannot be used for S1P because all previous cholesterol auxotrophs manifest defects in S2P, which is encoded by a single copy gene. To circumvent this problem, in the current studies we transfected Chinese hamster ovary cells with the S2P cDNA, assuring multiple copies. We mutagenized the cells, selected for cholesterol auxotrophy, and identified two mutant cell lines (SRD-12A and -12B) that fail to cleave SREBPs at site 1. Complementation analysis demonstrated that the defects in both cell lines are recessive and noncomplementing, indicating a mutation in the same gene. These cells should now be useful for expression cloning of the sterol-regulated S1P gene.

Acetates↗

Pharmacokinetics of doxacurium during normothermic and hypothermic cardiopulmonary bypass surgery.

PURPOSE: To compare the pharmacokinetic behaviour of doxacurium in patients undergoing normothermic or hypothermic cardiopulmonary bypass (CPB) for coronary artery bypass graft surgery. METHODS: Twenty patients in two equal groups were studied. Anaesthesia was induced with sufentanil and midazolam after a standard premedication. Doxacurium was administered at 3 x ED95 (80 micrograms.kg-1), and anaesthesia was maintained with 0.5 microgram.kg-1 hr-1 sufentanil, 0.05 mg.kg-1 midazolam and isoflurane 0.5-1%. Systemic temperature for patients in the normothermic and hypothermic groups was maintained at 33-36 C and 26-30 C respectively. Timed blood and urine samples were collected and pharmacokinetic parameters were estimated using a non-compartmental approach. RESULTS: For the normothermic and hypothermic groups, terminal elimination half-life (t1/2 beta) was 100.1 +/- 28 and 183.8 +/- 60 min (P < 0.05) respectively, elimination half-life during the CPB phase (T1/2 CPB) 114.5 +/- 10 and 183.8 +/- 60 min (P < 0.05), mean residence time 108.8 +/- 25 and 164.8 +/- 34 min (P < 0.05) and apparent volume of distribution at steady state 0.20 +/- 0.03 and 0.26 +/- 0.04 L.kg-1 (P < 0.05). Compared with the hypothermic group, the normothermic group had a higher rate of renal clearance (1.40 +/- 0.4 vs 0.93 +/- 0.3 ml.min-1.kg-1; P < 0.05) and a higher value for renal clearance as a percentage of the total clearance (76.2 +/- 10 vs 58.3 +/- 20%). CONCLUSION: The elimination rate of doxacurium during normothermic CPB is faster than that in hypothermic CPB.

Aged↗

MR imaging of the prostate and bladder.

Magnetic resonance imaging has become an important imaging modality for the male pelvis. Its unparalleled ability to depict soft tissue structures and highlight pathology have made it the best method for determining the extent of many disease processes. This article reviews the use of MR to evaluate diseases of the prostate gland and bladder. In both, the major indication for imaging is the local staging of cancer, and MR is currently the best imaging modality. This article will discuss the critical clinical issues concerning prostate cancer and neoplasms of the bladder, and the contribution of MR imaging.

Humans↗

Molecular identification of the sterol-regulated luminal protease that cleaves SREBPs and controls lipid composition of animal cells.

The lipid composition of animal cells is controlled by SREBPs, transcription factors released from membranes by sterol-regulated proteolysis. Release is initiated by Site-1 protease (S1P), which cleaves SREBPs in the ER luminal loop between two membrane-spanning regions. To clone S1P, we prepared pCMV-PLAP-BP2, which encodes a fusion protein that contains placental alkaline phosphatase (PLAP) in the ER lumen flanked by cleavage sites for signal peptidase and S1P. In sterol-deprived cells, cleavage by both proteases leads to PLAP secretion. PLAP is not secreted by SRD-12B cells, cholesterol auxotrophs that lack S1P. We transfected SRD-12B cells with pCMV-PLAP-BP2 plus pools of CHO cDNAs and identified a cDNA that restores Site-1 cleavage and PLAP secretion. The cDNA encodes S1P, an intraluminal 1052-amino-acid membrane-bound subtilisin-like protease. We propose that S1P is the sterol-regulated protease that controls lipid metabolism in animal cells.

Alkaline Phosphatase↗

Localization of hepatitis delta virus RNA in the nucleus of human cells.

Hepatitis delta virus (HDV) is a human pathogen that can greatly increase the severity of liver damage caused by an hepatitis B infection. HDV contains a circular, single-stranded RNA genome that encodes a unique protein, the delta antigen. Two forms of the delta antigen, deltaAg-S and deltaAg-L, are derived from a single open reading frame by RNA editing. Here we analyze the subcellular distribution of HDV RNA and its spatial relationship to known intranuclear structures. The human hepatoma cell line Huh7 was stably transfected with wild-type HDV cDNA and the viral RNAs were localized by in situ hybridization and fluorescence confocal microscopy. HDV RNA is detected throughout the nucleoplasm, with additional concentration in focal structures closely associated with nuclear speckles or clusters of interchromatin granules. Both the smaller form of the delta antigen (deltaAg-S), which is required for HDV genomic replication, and the larger form of the delta antigen (deltaAg-L), which represses replication, co-localize with delta RNA throughout the nucleoplasm and in the foci. However, the foci do not incorporate bromo-UTP and do not concentrate either RNA polymerase II or cleavage and polyadenylation factors required for viral RNA synthesis and 3' end processing, respectively. Thus, it is unlikely that the delta foci represent major sites of viral transcription or replication. In conclusion, the data show that viral RNA-protein complexes accumulate in structures closely associated with interchromatin granules, a subnuclear domain highly enriched in small nuclear ribonucleoproteins, poly(A+) RNA, and RNA splicing protein factors. This implies a specific compartmentalization of ribonucleoproteins in the nucleus.

Carcinoma, Hepatocellular↗

In vitro resistance to thrombin-induced platelet microbicidal protein among clinical bacteremic isolates of Staphylococcus aureus correlates with an endovascular infectious source.

Platelet microbicidal proteins (PMPs), small cationic peptides released at sites of endovascular damage, kill common bloodstream pathogens in vitro. Our group previously showed that in vitro resistance of clinical staphylococcal and viridans group streptococcal bacteremic strains to PMPs correlated with the diagnosis of infective endocarditis (IE) (Wu et al., Antimicrob. Agents Chemother. 38:729-732, 1994). However, that study was limited by (i) the small number of Staphylococcus aureus isolates from IE patients, (ii) the retrospective nature of the case definitions, and (iii) the diverse geographic sources of strains. The present study evaluated the in vitro PMP susceptibility phenotype of a large number of staphylococcemic isolates (n = 60), collected at a single medical center and categorized by defined and validated clinical criteria. A significantly higher proportion of staphylococcemic strains from patients with IE was PMP resistant in vitro than the proportion of strains from patients with soft tissue sepsis (83% and 33%, respectively; P < 0.01). Moreover, the levels of PMP resistance (mean percent survival of strains after 2-h exposure to PMP in vitro) were significantly higher for isolates from patients with IE and with vascular catheter sepsis than for strains from patients with abscess sepsis (P < 0.005 and P < 0.01, respectively). These data further support the concept that bloodstream pathogens that exhibit innate or acquired PMP resistance have a survival advantage with respect to either the induction or progression of endovascular infections.

Anti-Bacterial Agents↗

Scattering properties of Bagolini lenses and their effects on spatial vision.

The effect of a Bagolini lens on spatial vision was investigated by studying its far-field diffraction pattern as produced by a coherent beam of laser light, and its effect on the contrast sensitivity function (CSF) in human subjects. For lenses of the main type studied, which were crossed by a series of slightly-irregular striated bands, each consisting of fine, parallel, etched lines of various widths and separations, the diffraction pattern consisted of undiffracted light giving a bright central spot and wide-angle, diffracted light giving a dim streak. The latter was due to the sum of the diffraction patterns associated by the irregular fine etched lines. The streak produced by a single striated band was modulated by a series of regular maxima and minima related to the width of the band. Analysis of this pattern gave the width of the band as 0.6 mm, in close agreement with direct microscopical measurements. When four bands were illuminated by a beam of about 3 mm diameter, similar to the diameter of the photopic pupil, the diffraction pattern showed no obvious maxima and minima, due to irregularity in the width and separation of the bands. The central spot contained more than 90% of the total light in the diffraction pattern. Thus the Bagolini lens, with its relatively weak far-field diffraction pattern lacking regular maxima and minima when areas > or = 3 mm in diameter were used, was expected to have only a small effect on the apparent contrast of the targets in CSF experiments. This was confirmed by the measurements: Bagolini lenses showed no significant effect on either the monocular or binocular CSF. Further similar measurements with lenses of slightly different design from another manufacturer confirmed these findings. Therefore Bagolini lenses do not disrupt vision when they are used to determine the presence of suppression and anomalous retinal correspondence.

Contrast Sensitivity↗