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Biomedical subjects

D S Cheng

Publications and source records attributed to D S Cheng.

At least 19 recordsLinked to original sources

FKBP binding characteristics of cardiac microsomes from diverse vertebrates.

FK506 binding protein (FKBP) is a cytosolic receptor for the immunosuppressive drug FK-506. The common isoform, FKBP12, was found to be associated with the calcium release channel (ryanodine receptor 1) of different species of vertebrate skeletal muscle, whereas 12.6, a novel FKBP isoform was found to be associated with canine cardiac ryanodine receptor (ryanodine receptor 2). Until recently, canine cardiac sarcoplasmic reticulum was considered to be the prototype for studying heart RyR2 and its interactions with FKBP. In this study, cardiac microsomes were isolated from diverse vertebrates: human, rabbit, rat, mice, dog, chicken, frog, and fish and were analyzed for their ability to bind or exchange with FKBP isoforms 12 and 12.6. Our studies indicate that RyR2 from seven out of the eight animals contain both FKBP12 and 12.6. Dog is the exception. It can now be concluded that the association of FKBP isoforms with RyR2 is widely conserved in the hearts of different species of vertebrates.

Animals↗

Pleural fluid characteristics of patients with symptomatic pleural effusion after coronary artery bypass graft surgery.

BACKGROUND: This study describes the pleural fluid characteristics of patients who develop symptomatic pleural effusions after coronary artery bypass graft surgery (CABG). METHODS: Post-CABG patients who underwent a therapeutic thoracentesis for a symptomatic pleural effusion were included unless another explanation for the pleural effusion was present. RESULTS: During the study, 71 patients (mean age, 61 years) were identified; 49 were men and 22 were women. All patients underwent internal mammary artery grafting. Early effusions (<30 days after CABG) occurred in 45 patients (63%) and late effusions (>/=30 days after CABG) developed in 26 (37%). Early effusions were bloody (median red blood cell count, 706 x 10(12)/L [706,000 mm(3)])with a high eosinophil count (median, 0.385), whereas effusions that occurred in the late period were yellow exudates with predominant lymphocytes (median, 0.68) and monocytes (median, 0.20). The mean pleural fluid level of lactate dehydrogenase was more than 3 times the upper limit of the reference range in serum in early effusions, whereas late effusions had significantly lower lactate dehydrogenase levels. CONCLUSIONS: Characteristics of early and late effusions differ significantly, suggesting a different pathogenesis of the effusions. Patients who develop a symptomatic pleural effusion after CABG should undergo a therapeutic thoracentesis; however, further investigations are warranted only in patients who have pleural fluid characteristics different from those described.

Aged↗

The effects of intrapleural polyclonal anti-tumor necrosis factor alpha (TNF alpha) Fab fragments on pleurodesis in rabbits.

The mechanism by which various agents produce a pleurodesis is unknown. The purpose of this project was to determine whether the pleurodesis that results from the intrapleural administration of talc or doxycycline depends on tumor necrosis factor alpha (TNF alpha). In a randomized, blinded, placebo-controlled study, 34 New Zealand white rabbits were given 400 mg talc or 10 mg/kg doxycycline intrapleurally as a sclerosant through a chest tube. Half the rabbits in each group were also given 2,000 units of ovine, polyclonal affinity purified anti-TNF alpha Fab, or saline as placebo immediately after and 12 h after the injection of the sclerosant. Chest tubes were aspirated at 12-h intervals until their removal at 4 days. Rabbits were killed at 28 days. The pleural fluid volume, cell counts, lactate dehydrogenase (LDH) and pleurodesis scores were compared among groups. Both talc and doxycycline produced an exudative pleural effusion. The pleural fluid volume and the pleural fluid LDH levels were significantly (p < 0.05) greater in the group given doxycycline. The administration of anti-TNF alpha Fab had no significant effect on pleural fluid volume or leukocyte count in either group. However, the administration of anti-TNF alpha Fab resulted in a significant decrease (p = 0.004) in the pleurodesis score for the animals given talc (3.2 +/- 0.8 without Fab and 1.8 +/- 0.9 with Fab). In contrast, the pleurodesis score was virtually identical in the doxycycline group with (3.5 +/- 0.5) and without (3.4 +/- 0.7) Fab. The administration of anti-TNF alpha Fab diminishes the pleurodesis induced by talc but not that resulting from doxycycline. These findings suggest that different mechanisms are involved with the two different sclerosants.

Animals↗

Adenovirus-mediated lymphotactin gene transfer improves therapeutic efficacy of cytosine deaminase suicide gene therapy in established murine colon carcinoma.

Lymphotactin (Ltn) is the sole member of C chemokines which attracts T cells and NK cells specially. Ltn gene was transferred in vivo to improve the antitumor efficacy of cytosine deaminase (CD) gene therapy. Upregulation of CD80 and CD54 on murine CT26 colon carcinoma cells was observed after combined transfection with adenovirus encoding CD (AdCD) and adenovirus encoding murine Ltn (AdLtn) followed by administration of 5-fluorocytosine (5FC) in vitro. AdCD/5FC treatment also increased the expression of CD95 and induced obvious apoptosis of CT26 cells. After combined treatment with AdLtn and AdCD/5FC, the pre-established murine model with subcutaneous CT26 colon carcinoma exhibited most significant tumor growth inhibition, and four of eight tumor-bearing mice were tumor free, while tumors in other mice grew more progressively. Examination of lymphocyte infiltration and cytokine gene expression in tumor tissue revealed that tumors from AdLtn/AdCD/5FC-or AdLtn-treated mice were heavily infiltrated with CD4+, CD8+ T cells and NK cells, and IL-2 and IFN-gamma mRNA expression were present in parallel with T cell and NK cell infiltration. Splenic NK and CTL activities increased significantly after the combination therapy. In vivo depletion analysis showed that NK cells, CD4+ T cells and CD8+T cells participated in the antitumor effect of the host with CD8+T cells being the main T cell subset responsible for the enhanced antitumor immune response. These findings suggested that increased immunogenicity and induction of apoptosis of the tumor cells, and efficient induction of local and systemic antitumor immunity of the host might contribute to the enhanced antitumor effects of the combined Ltn and CD suicide therapy. Gene Therapy (2000) 7, 329-338.

Adenoviridae↗

A single intrapleural injection of transforming growth factor-beta(2) produces an excellent pleurodesis in rabbits.

The purpose of the present study was to determine whether the intrapleural injection of transforming growth factor beta(2) (TGF-beta(2)) would produce a pleurodesis in rabbits. Single intrapleural injections of TGF-beta(2) at doses of 5.00 microg (n = 12), 1.67 microg (n = 10), 0.50 microg (n = 10), or 0.167 microg (n = 4), or of the parenteral buffer alone (n = 5) were given in a volume of 2 ml to New Zealand white rabbits. Chest tubes were left in place for at least 72 h. Pleural fluid was aspirated at 24-h intervals and was measured and subjected to chemical analysis. The animals were killed 14 d after the injection. The intrapleural injection of TGF-beta(2) resulted in a dose-dependent pleurodesis (on a scale of 0 to 4, where 0 = no pleurodesis and 4 = complete pleurodesis) with mean scores of 3.6, 2.6, 1.5, 0.7, and 0.3 for the groups that received 5.0, 1.67, 0.50, and 0.167 microg of TGF-beta(2) and buffer alone, respectively. Intrapleural injection of the larger doses of TGF-beta(2) resulted in the formation of a large amount of pleural fluid. The fluid had a significantly lower white blood cell (WBC) count and lactate dehydrogenase (LDH) level than did the fluid that results from the intrapleural injection of 10 mg/kg doxycycline or 400 mg/kg talc slurry. On the basis of this study we conclude that a single intrapleural injection of TGF-beta(2) induces pleurodesis in a dose-dependent manner. A dose of 5.0 microg produced satisfactory pleurodesis in almost all of the rabbits so treated. Larger doses of TGF-beta(2) induced larger pleural effusions with relatively low pleural fluid WBC counts and LDH levels. The ability of TGF-beta to produce a pleurodesis in patients with recurrent pleural effusions or pneumothorax should be investigated. A single intrapleural injection of TGF-beta(2) may produce a pleurodesis both safely and painlessly.

Animals↗

Human dynamin-like protein interacts with the glycogen synthase kinase 3beta.

Members of the dynamin superfamily are implicated in vesicle trafficking. Using human glycogen synthase kinase 3 beta (Gsk-3 beta) as bait in the yeast two-hybrid system, we identified a novel human dynamin-like protein IV (HdynIV). When the full-length cDNA of HdynIV was sequenced, it showed that HdynIV's carboxyl terminal lacks a proline-rich domain that can bind to Gsk-3 beta. By Northern blot analysis and isoform-specific PCR, we found that HdynIV is expressed ubiquitously in all human tissues examined. Two transcripts of 2.4 and 4.4 kb are shown to be more abundant in heart, brain, and skeletal muscle. Interestingly, the 2.4-kb transcript is expressed more distinctly in the fetal liver than in the adult liver, suggesting that this protein might play a role during development. In the present report, we have demonstrated that HdynIV interacts with the Gsk-3 beta through its carboxyl-terminal region, implying than HdynIV may also be involved in cell signaling.

Adult↗

Carbon dioxide laser surgery for snoring: results in 192 patients.

Laser-assisted uvulopalatoplasty has been introduced as an alternative to uvulopalatopharyngoplasty for treatment of snoring and potentially of obstructive sleep apnea syndrome. Between July 1994 and June 1996, 192 patients underwent 227 laser-assisted uvulopalatoplasty procedures. Loud habitual snoring was evaluated in 42 women (21.8%) and 150 men (78.2%), who were then treated with laser-assisted uvulopalatoplasty. Among the 192 patients (227 procedures), with ages from 18 to 81 years (mean 42.6 years), 15.6% (30 patients) had more than one laser-assisted uvulopalatoplasty treatment. In our series, 80 patients (42.1%) had a history of obstructive sleep apnea syndrome in addition to snoring. Laser-assisted uvulopalatoplasty treatment in patients with loud snoring resulted in elimination of snoring in 61%, partial improvement of snoring in 26%, and no improvement in 13%. The overall success rate was 87%. The mean body mass index was significantly higher in the patients with no response after the operation (27.9 kg/m2) compared with that in the patients with a good response (25.9 kg/m2). Obese (body mass index >30 kg/m2) patients were more likely to have no response to laser-assisted uvulopalatoplasty treatment of snoring than patients with an ideal body weight (body mass index <25 kg/m2) (p < 0.01). We conclude that the body mass index may be of significant value in the postoperative success rate of laser-assisted uvulopalatoplasty for the treatment of snoring.

Adolescent↗

Comparison of pleural fluid pH values obtained using blood gas machine, pH meter, and pH indicator strip.

STUDY PURPOSE: The purpose of this study was to compare the pleural fluid pH values obtained with a blood gas machine (pHbg), with a pH meter (pHmet), and with a pH indicator strip (pHstrip), to determine if the pleural fluid pH measured by a pH meter or a pH indicator strip was sufficiently accurate for clinical decisions. METHODS: The pleural fluid pH was determined, within 20 min after being collected anaerobically, by a blood gas machine (CIBA-Corning model 288), pH meter (Corning pH meter 610A), and pH indicator strip (Baxter Diagnostic) following routine laboratory procedures in 50 pleural fluids. Pleural fluid pH was determined in seven additional samples with the blood gas machine and a pH meter at 25 and 37 degrees C respectively, initially, and after 30 min. RESULTS: The mean pHbg (7.42+/-0.01) was significantly less than the mean pHmet (7.58+/-0.02) or the mean pHstrip (8.23+/-0.06). There were significant differences between the pHbg and the pHmet (p < 0.001), and between the pHbg and the pHstrip (p < 0.001). Analysis of the additional seven samples demonstrated that when the blood gas machine was set at 25 degrees C, the pHbg (pHbg = 7.54+/-0.02) and the pHmet (7.53+/-0.01) were almost identical. CONCLUSION: When the pleural fluid pH is going to be used for decision making, only the pH values provided by the blood gas machine are sufficiently accurate.

Blood Gas Analysis↗

Long-term results of toe transfer: retrospective analysis.

Between February 1966 and February 1994, 400 cases of toe transplantation were analyzed, to evaluate toe-transfer procedures in thumb and finger reconstruction. Techniques utilized included single second-toe transfer, with and without the metatarsophalangeal joint (299): second- and third-toe transfer (28); second-toe and third proximal phalanx transfer (1); second-toe with flap transfers (66); and hallux nail flap with second toe or second and third toe transfer (6). There was a survival rate of 96.5 percent, with 386 cases surviving and 14 failing. A more than 2-year follow-up was possible in 240 cases. Excellent motor and sensory function (more than 90 percent of normal) was achieved in the reconstructed fingers and thumbs, as well as satisfactory function (between 86 and 91 percent of normal) in the donor foot.

Adolescent↗

Free toe transfer for thumb and finger reconstruction in 300 cases.

From 1966 to 1989, we performed free toe transfer for thumb and finger reconstruction in 300 patients, with 286 survivals and 14 failures, a total survival rate of 95.55 percent. Follow-up for 2 to 23 years showed that movement and sensation of the reconstructed thumbs and fingers were satisfactory in all of the 286 cases. The optimal indications for the operation were defect of the thumb at the plane of the metacarpophalangeal joint and defects of the second to fifth fingers. Besides atraumatic isolation of the second toe and sophisticated microsurgical suturing technique, special attention was paid to intraoperative vascular variations, to providing the double arterial blood supply system if necessary, and to the identification and management of postoperative circulatory crisis.

Adult↗

Nonoperative management of femoral, humeral, and acetabular metastases in patients with breast carcinoma.

A retrospective analysis of 59 cases of metastatic breast carcinoma involving the long bones and acetabula was done in an attempt to determine the role of radiation therapy in the management of bone metastases. A total of 97 bone lesions were treated with radiation as the initial therapeutic modality. Seven patients had pathologic fractures when first seen, and 2 had sustained fractures while receiving radiation therapy, and 2, following completion of radiation therapy. All patients had pain relief and improvement in their performance status. A third of patients had radiographic evidence of bone healing. None of the high-risk lesions that may ordinarily be subjected to prophylactic orthopedic stabilization in many medical centers sustained a pathologic fracture after the completion of radiation therapy. We conclude that the use of radiation therapy in initial management of bone metastases in patients with breast cancer is usually effective, and that prophylactic surgical intervention is not warranted in most cases.

Acetabulum↗

Idiopathic myelofibrosis without splenomegaly.

The patient described has had idiopathic myelofibrosis for 8 years. At the time of presentation, 12% of the circulating white cells were myeloblasts. In the past two years, the white blood count has been as high as 18,000/mm3 with 50% myeloblasts. Of significance is the absence of splenomegaly over the eight year period of observation. The rarity of the absence of significant splenomegaly and the presence of large numbers of circulating myeloblasts in idiopathic myelofibrosis are reviewed.

Aged↗

Idiopathic refractory sideroblastic anemia: incidence and risk factors for leukemic transformation.

The clinical course of 29 patients with idiopathic refractory sideroblastic anemia studied by us was reviewed. Four patients developed acute leukemia. We were able to find 27 out of 268 cases of idiopathic refractory sideroblastic anemia reported in the literature which terminated in acute leukemia. Nine of these were well described. The overall incidence of acute leukemia is 10%. In an attempt to identify the risk factors for the development of acute leukemia, the clinical and laboratory features of this group of thirteen well-described cases which terminated in acute leukemia were compared to the remaining 25 of our cases which did not undergo leukemic transformation. The patients who died of acute leukemia tended to have a more severe anemia, a lower reticulocyte count, and increased transfusion requirement, and thrombocytopenia. Thrombocytosis appears to be a relatively good prognostic sign.

Adult↗

Chronic granulocytic leukemia: long-term remission in a patient with familial sarcoidosis.

A patient is described who has chronic granulocytic leukemia (CGL) and familial sarcoidosis, and who has been in complete remission for six years after a single course of busulfan therapy. Her bone marrow Philadelphia chromosome persists and the leukocyte alkaline phosphatase activity remains subnormal. Leukocyte alkaline phosphatase levels in nine white patients with sarcoidosis were all found to be low. Bone marrow chromosomes from two patients with active sarcoidosis showed no Philadelphia chromosome, but one of them, and our patient with CGL, exhibited a pericentric inversion of chromosome 9.

Alkaline Phosphatase↗

DNA content in nasopharyngeal carcinoma.

DNA analysis by flow cytometry was performed on tissue blocks from 41 patients with nasopharyngeal carcinoma. The histologic slides were reviewed by a pathologist and blindly classified according to the World Health Organization classification. The paraffin-embedded blocks were processed to obtain individual nuclei, which were then stained with propidium iodide. The nuclei were analyzed on a flow cytometer. Excluding 10 uninterpretable histograms, the remainder were interpreted blindly and classified as diploid or aneuploid. The Cox proportional hazards survival model was used to analyze stage, histology, radiation dose, and ploidy. We observed more diploids (23 of 31; 74%) than aneuploids (eight of 31; 26%). The 2-year survival rate of diploids was 55%, compared with 25% of aneuploids (P less than .05). We conclude that ploidy status is an independent prognostic factor in nasopharyngeal carcinoma.

Carcinoma↗