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Biomedical subjects

J C Yang

Publications and source records attributed to J C Yang.

At least 145 records · Page 8Linked to original sources

Long-term outcome in 87 patients with low-grade soft-tissue sarcoma.

OBJECTIVE: To describe the long-term clinical outcome of patients with low-grade soft-tissue sarcoma and identify factors that may predict or determine their prognosis. DESIGN: Retrospective chart review with multivariate analysis. SETTING: Large research hospital and referral center. PATIENTS: All patients treated between 1975 and 1990 at the National Cancer Institute (Bethesda, Md) who had a confirmed diagnosis of low-grade soft-tissue sarcoma. INTERVENTIONS: Surgery and radiation therapy. MAIN OUTCOME MEASURES: Local recurrence and overall survival. RESULTS: For patients with nonretroperitoneal lesions, overall survival was excellent, with a history of recurrence, a positive surgical margin, and an absence of adjuvant radiation therapy significantly associated with increased risks of local recurrence. Patients with retroperitoneal lesions not only had an increased risk of local recurrence, but significantly poorer overall survival. CONCLUSIONS: Low-grade soft-tissue sarcomas are associated with excellent overall survival, especially those confined to nonretroperitoneal sites. The risk of local recurrence after resection with negative margins and/or adjuvant radiation therapy is very low and most recurrences can be controlled with further therapy.

Adolescent↗

Detection of Helicobacter pylori in gastric biopsy tissue by polymerase chain reaction.

To evaluate the sensitivity of a polymerase chain reaction (PCR) assay using nested primers in detecting Helicobacter pylori, gastric tissue biopsy specimens were collected on endoscopy from 17 patients with a duodenal ulcer. DNA was extracted by phenol/chloroform treatment or boiling in water, and then subjected to a nested PCR using two primer pairs from the urease gene of Helicobacter pylori. Fourteen of the 17 patients were positive for Helicobacter pylori using DNA samples extracted by either method. The PCR results correlated well with the results of an enzyme immunoassay to detect IgG antibody. However, there were two culture negative patients. The three PCR negative patients were both culture negative and serologically negative. DNA from 9 of the 14 patients was randomly selected and subjected to semiquantification by serial dilutions, and then PCR. The results showed that phenol/chloroform extraction yielded 10-1000 times more DNA than the boiling method. It is concluded that the PCR assay is a rapid and sensitive method for detecting Helicobacter pylori, and that phenol/chloroform extraction is superior to simple boiling in obtaining DNA samples for PCR.

Antibodies, Bacterial↗

Combination chemoimmunotherapy for metastatic colorectal cancer using 5-fluorouracil, leucovorin and interleukin-2.

25 patients with metastatic colorectal cancer were entered into a phase II trial of combination chemoimmunotherapy using a sequential regimen of 5-fluorouracil (5-FU) and leucovorin and high-dose recombinant human interleukin-2 (rIL-2). Patients initially received three cycles of chemotherapy consisting of 500 mg/m2 of intravenous leucovorin followed by 375 mg/m2 of bolus 5-FU both given daily on days 1-5 of a 21 day cycle. Ten days after the last dose of chemotherapy in cycle 3, patients began high-dose rIL-2 at 720,000 IU/kg intravenously every 8 h to the maximum tolerated number of doses. After 7-10 days of recovery, this rIL-2 treatment was repeated to complete one full course of chemoimmunotherapy. There was no grade IV toxicity associated with 183 cycles of chemotherapy. Other than slight increases in the frequency of diarrhoea, stomatitis and hyperbilirubinaemia, rIL-2 toxicity was similar to that seen in patients given rIL-2 without chemotherapy. Of 23 evaluable patients, the overall response rate (partial + complete response) was 46% with 2 complete responses. Only 3 patients showed major tumour regression during the rIL-2 phase of therapy, but these 3 patients included both complete responders and the 3 most durable responses (15, 16 and 24 months). We conclude that sequential 5-FU/leucovorin and rIL-2 can be given safely without major increases in toxicity over either therapy alone, and although nearly all responses seen are largely attributable to chemotherapy, a contribution of immunotherapy to the minority of patients achieving complete or durable responses cannot be ruled out.

Adult↗

Percutaneous transcystic cholangioscopy for combined treatment of gallbladder and bile duct stones.

A procedure for percutaneous transcystic cholangioscopy requiring only one percutaneous transhepatic fistulous tract to remove stones located in both the gallbladder and bile ducts is described. The procedure begins with percutaneous transhepatic drainage of the gallbladder or bile duct. Stones in the gallbladder and bile duct can be removed under direct vision on transhepatic cholangioscopy. Larger stones can be fragmented by electrohydraulic lithotripsy before removal. In a preliminary trial the procedure proved to be a feasible method for treatment of 13 patients with both gallbladder and bile duct stones as well as septic cholangitis who either refused operation or were considered poor candidates for surgery. On long-term follow-up (mean period 28 months) stone recurrence was observed in three patients.

Aged↗

The development of gene therapy for the treatment of cancer.

OBJECTIVE: The authors sought to develop new treatments for patients with cancer based on the genetic modification of immune lymphocytes and tumor cells designed to increase the host immune reaction against growing cancers. METHODS: Retroviral-mediated gene transduction was used to introduce genes into tumor-infiltrating lymphocytes (TIL), and these genetically altered TIL were administered to patients with cancer. Genes coding for cytokines were introduced into tumor cells, and these cells were used to immunize patients against their autologous cancers. RESULTS: In initial studies, the gene for neomycin phosphotransferase was introduced into the TIL of ten patients with advanced cancer to study the survival and distribution of TIL in humans. These studies showed that retroviral gene transduction is a safe and practical method for adding genes to human cells and led to clinical trials in which the gene for tumor necrosis factor (TNF) was inserted into TIL in an effort to increase their therapeutic effectiveness. Phase I trials are currently underway using TIL that secrete up to 100 times the normal level of TNF. More recently, animal experiments have revealed that transduction of tumor cells with cytokine genes can enhance tumor immunogenicity and, thus, increase the recognition of the tumor as foreign by the host. Clinical trials based on these observations have begun in which patients are immunized against their own autologous tumors that were transduced with the genes for TNF or interleukin-2. CONCLUSIONS: Attempts at gene therapy for cancer are underway and have opened new possibilities for the development of cancer treatments.

Adult↗

Phase I trial of subcutaneous interleukin-6 in patients with advanced malignancies.

PURPOSE: Based on preclinical evidence in murine models that interleukin-6 (IL-6) mediates regression of metastatic tumors, we performed a phase I study of recombinant human IL-6 in patients with refractory advanced malignancies to determine its pharmacokinetics, toxicities, and possible immunologic and antitumor effects. PATIENTS AND METHODS: Recombinant IL-6 was administered as a single subcutaneous dose daily for 7 days, with 7 days off therapy followed by another 7 days of IL-6. Doses were escalated in cohorts of three patients starting at 3 micrograms/kg/d, provided that toxicity at the preceding dose level was not dose-limiting. Dose-limiting toxicity was defined as grade III or IV major organ toxicity that did not resolve to grade II or less in 24 hours after stopping IL-6, using the National Cancer Institute Common Toxicity Criteria. Patients were treated with 3, 10, and 30 micrograms/kg/d IL-6 subcutaneously. RESULTS: Three patients each were treated at the 3- and 10-micrograms dose levels. Two of five patients treated with 30 micrograms/kg/d IL-6 subcutaneously had grade III major organ toxicity that required IL-6 therapy to be discontinued. All patients experienced fever, chills, and minor fatigue. Significant increases in C-reactive protein (CRP), fibrinogen, platelet counts, and lymphocyte IL-2 receptor levels were seen in patients at the 10- and 30-micrograms/kg dose levels. Decreases in albumin and hemoglobin were observed, particularly at the 30-micrograms/kg dose level. The half-life (T1/2 beta) was 4.2 hours, with a peak IL-6 level at 5 hours. No antitumor responses were seen. CONCLUSION: A safely tolerated dose of daily subcutaneous IL-6 is 10 micrograms/kg, with hepatotoxicity and cardiac arrhythmia being the dose-limiting toxicities at 30 micrograms/kg. Phase II trials of IL-6 administered subcutaneously daily for at least 7 days for two cycles with an intervening week of rest are recommended for phase II trials. However, patients with extensive replacement of liver by tumor and abnormal liver functions should receive IL-6 therapy with caution.

Acute-Phase Proteins↗

[The study of anatomic factors in difficult intubations].

Endotracheal intubation is a common procedure in anesthesia which can usually be accomplished easily. However if the attempt is unexpectedly difficult the patient may be seriously at risk. If all difficult airways can be predicted confidently in the pre-operative period, anesthesiologists can plan the safest and most effective way of managing tracheal intubation. The purpose of this study was to analyze not only the incidence, anatomic factors, immediate complications and management of difficult intubation cases but also the view obtained at laryngoscope which was graded according to the Cormack's and Lehane's description. Patients who received general anesthesia with endotracheal tube within 1 year's period from November 1, 1991 to October 31, 1992 in Show Chwan Memorial Hospital were collected. All difficult intubations were performed by senior anesthesiologists. 3925 patients were intubated, 92 cases were noted to have difficult intubations and their overall incidence were 2.3%. Among the 92 patients, those with 2 anatomic factors (41 patients, 44.6%) represented the majority for patients with difficult intubations. On the other hand, the four most common anatomic factors and their incidences in order of frequency included short neck (48.9%), protruding teeth (38.0%), receding mandible (27.2%) and limited opening mouth (26.1%). According to Cormack's and Lehane's laryngoscopic grading, the results were shown respectively as follow: 4 cases (4.4%) for grade 1;2 cases (2.2%) for grade 2;82 case (89%) for grade 3 and 4 cases (4.4%) for grade 4. We also found that tachycardia/hypertension (70.7%), bleeding (37.0%) and esophageal intubation (33.7%) were the three most frequent immediate complications during difficult intubations.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

A tumor-elaborated supernatant factor chemotactic for IL-2 expanded tumor infiltrating T-lymphocytes.

Very little is known about factors influencing the migration of highly activated T-lymphocytes. One such lymphocyte population is the IL-2 expanded population of T cells infiltrating tumors. These tumor-infiltrating lymphocytes (TIL) can cause tumor regression in patients with metastatic cancer and in murine tumor models when given in adoptive transfer. In patients with melanoma, these TIL have been shown to migrate to sites of tumor and this may be a critical factor in their antitumor activity. In this study, a 48-well microchemotaxis chamber and a 5 microns pore nitrocellulose filter membrane system was utilized to study the motility of murine TIL. A chemotactic response was observed to supernatants from freshly explanted, autologous, and nonautologous tumor cultured for 24 h. Serially passaged autologous and nonautologous tumors also produced supernatants with chemotactic activity. Supernatants from single cell suspensions of normal tissues prepared and cultured identically did not elicit chemotaxis. Chemotactic activity for TIL was not removed by dialysis (2000 MW exclusion limit), its activity was undiminished by heat treatment at 60 degrees C for up to 60 min, and it was trypsin sensitive. Tumor supernatants were also chemotactic for two IL-2-dependent specifically alloreactive CTL lines (CTL-TIM and OE-4), but not two helper T cell lines (D-10 and D-1.5) or normal resting lymphocytes. This is the first demonstration of a chemotactic effect on IL-2-dependent, activated T cells. Characterization and purification of factors from tumor responsible for this directed migration are in progress.

Animals↗

Determination of the solution structures of domains II and III of protein G from Streptococcus by 1H nuclear magnetic resonance.

We have used 1H nuclear magnetic resonance spectroscopy to determine the solution structures of two small (61 and 64 residue) immunoglobulin G (IgG)-binding domains from protein G, a cell-surface protein from Streptococcus strain G148. The two domains differ in sequence by four amino acid substitutions, and differ in their affinity for some subclasses of IgG. The structure of domain II was determined using a total of 478 distance restraints, 31 phi and 9 chi 1 dihedral angle restraints; that of domain III was determined using a total of 445 distance restraints, 31 phi and 9 chi 1 dihedral angle restraints. A protocol which involved distance geometry, simulated annealing and restrained molecular dynamics was used to determine ensembles of 40 structures consistent with these restraints. The structures are found to consist of an alpha-helix packed against a four-stranded antiparallel-parallel-antiparallel beta-sheet. The structures of the two domains are compared to each other and to the reported structure of a similar domain from a protein G from a different strain of Streptococcus. We conclude that the difference in affinity of domains II and III for IgG is due to local changes in amino acid side-chains, rather than a more extensive change in conformation, suggesting that one or more of the residues which differ between them are directly involved in interaction with IgG.

Bacterial Proteins↗

Surgical resection of metastatic renal cell carcinoma and melanoma after response to interleukin-2-based immunotherapy.

Thirty-one patients with disseminated melanoma or renal cell cancer (RCC) who had a limited relapse or persistent disease after a partial or complete response to interleukin-2 (IL-2)-based immunotherapy underwent resection of progressing tumors or residual sites of disease. There were no surgery-related deaths. The median time to disease progression after resection for patients with RCC (n = 16) and melanoma (n = 15) was 11 and 5 months, respectively. All patients with melanoma had tumor progression within 10 months of surgery. Seven of 16 patients with RCC were free of tumor progression 4 to 44 months after surgery. Three of 12 patients with RCC rendered disease-free by surgery remain disease-free after 2 years. These data suggest that surgical resection is a reasonable option in selected patients who have a relapse after responding to IL-2-based immunotherapy. Although this retrospective study could not determine the relative survival benefits of surgery and immunotherapy, it showed that resection of metastatic disease after a response to immunotherapy can result in significant disease-free survival in patients with RCC but not melanoma.

Carcinoma, Renal Cell↗

Sequence-specific resonance assignment and conformational analysis of subtilin by 2D NMR.

Subtilin, a 32-amino acid peptide with potent antimicrobial activity, has been isolated from Bacillus subtilis ATCC6633. The chemical structure has been confirmed by the unambiguous sequence-specific assignment of its 1H NMR spectrum. Detailed NMR analysis revealed that subtilin is a rather flexible molecule; the only observed conformational contraints were those imposed by the cyclic structures created by the lanthionine and 3-methyllanthionine residues. These results suggest that in aqueous solution subtilin and the homologous peptide nisin have similar conformations.

Amino Acid Sequence↗

Debrisoquine metabolism in Chinese patients with Alzheimer's and Parkinson's diseases.

We determined the oxidative phenotype and metabolic ratio of debrisoquine in 96 Chinese patients with Alzheimer's disease (n = 12), Parkinson's disease (n = 55), and using patients with stroke and cervical spondylosis as controls (n = 29). We did not find any difference in debrisoquine metabolic phenotype among Parkinson's disease, Alzheimer's disease, and control patients as judged by chi-square analysis. In addition, the metabolic ratio of all our patients was less than 12.6. The result suggested that Chinese patients with Parkinson's disease and Alzheimer's disease metabolize debrisoquine at a velocity not different from that of their Western counterparts even though the frequency distribution of debrisoquine metabolism phenotyping in these two populations is quite different.

Aged↗

Catheter optimization during contrast ventriculography: a prospective randomized trial.

Although newer contrast mediums have improved hemodynamic stability during left ventriculography, the image quality and hence the diagnostic yield of the procedure is largely determined by the choice of catheter and injection technique. In this study 125 patients were prospectively assigned at random to undergo ventriculography using either of two pigtail catheters, one with a straight shaft throughout its length (straight) and one with a 145-degree bend placed 6.5 cm from the distal end (angled). Injectate composition, flow rate, and volume were held constant for all injections, and baseline clinical and catheterization variables were found to be similar in each group. The angled catheter exhibited a statistically superior ease of insertion (p = 0.038) and took less time to position (p = 0.012), saving a mean of 23 seconds of fluoroscopy time per procedure. It was also associated with superior contour edge definition (p = 0.037) and a trend toward more uniform distribution of contrast medium (p = 0.089). Compared with the straight catheter, the angled catheter was less frequently accompanied by artifactual mitral regurgitation (p = 0.038) but was equally likely to provoke ventricular arrhythmias during injection. These observed differences may be explained in part by the tendency for angled catheters to more frequently localize in the central as opposed to the inferoposterior region of the left ventricular cavity (mean distance from center = 0.53 vs 1.10 cm, respectively; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Immunotherapy with interleukin-2 and alpha-interferon in patients with metastatic renal cell cancer with in situ primary cancers: a pilot study.

A total of 12 patients with stage 4 renal cell carcinoma and primary renal tumors in situ was entered into a pilot study using treatment with interleukin-2 and alpha-interferon followed by radical nephrectomy. Of the patients 11 underwent nephrectomy after an initial course of immunotherapy. Ten patients were able to receive a second course of immunotherapy given after nephrectomy. One patient achieved a complete response of lung and mediastinal metastases without any change in the primary renal tumor but after nephrectomy the patient remained in complete remission for greater than 11 months. A total of 3 patients achieved a partial response at some extrarenal sites but they had progression elsewhere. Toxicity was similar to previous experience with this immunotherapy regimen. Therefore, we demonstrated that metastatic tumor regression is possible with primary renal tumors in situ and that aggressive interleukin-2-based immunotherapy can be tolerated in the presence of a large renal tumor.

Adult↗

A pilot study of the combination of interleukin-2-based immunotherapy and radiation therapy.

A clinical trial was undertaken to evaluate the feasibility of combining radiation therapy and immunotherapy. Twenty-eight patients with metastatic cancer were treated with rapid fractionation radiation up to 2,000 cGy, followed within 24 h by a course of interleukin 2 (IL-2) at 720,000 IU/kg or tumor-infiltrating lymphocytes (TILs) and IL-2 at 720,000 IU/kg. All patients tolerated treatment without any apparent increase in toxicity referable to the irradiation. Four patients had significant shrinkage of tumor at the irradiated site. Only two patients showed significant tumor shrinkage both inside and outside of the irradiated field. While rapid fractionation radiation can be safely administered in combination with immunotherapy, we observed no apparent synergy in antitumor effect in this small number of patients.

Adult↗

Worldwide legal requirements for obtaining corneas: 1990.

Cornea transplantation offers the hope of restoring useful vision to millions of individuals worldwide. Yet it is widely used only in certain countries. While a lack of the necessary economic and technical infrastructure is the primary reason in many countries, the legal and social systems pose a similar obstacle in many other more prosperous countries. This article reviews the current laws governing organ and tissue donation throughout the world and distinguishes those that are most successful in obtaining tissue for transplantation.

Cornea↗