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Biomedical subjects

J C Yang

Publications and source records attributed to J C Yang.

At least 55 records · Page 3Linked to original sources

Serum endostatin levels are elevated and correlate with serum vascular endothelial growth factor levels in patients with stage IV clear cell renal cancer.

Clear cell renal carcinoma (CCRC) is a highly angiogenic tumor known to secrete vascular endothelial cell growth factor (VEGF). Endostatin is an endogenous antiangiogenic agent with antitumor activity in mice. The purpose of this study was to evaluate serum levels of endostatin in normal subjects and in patients with CCRC and to examine the relationship of these levels to circulating VEGF levels. Fifteen patients (mean age, 48 years) on a clinical protocol for stage IV CCRC at the National Cancer Institute were included in the study. Archived prenephrectomy serum samples were analyzed for endostatin and VEGF concentrations. Endostatin and VEGF levels were compared with those of an age-matched group of volunteer blood donors (n = 18) using a competitive enzyme immunoassay. Data were analyzed using the Mann-Whitney U test and the Spearman rank correlation. Median serum endostatin levels were 24.6 ng/ml (range, 15.1-54.0 ng/ml) in CCRC patients versus 14.1 ng/ml (range, 1.0-19.3 ng/ml) in healthy controls (P < 0.0001). Median VEGF levels were 3.4 ng/ml (range, 0.1-11.2 ng/ml) and 2.5 ng/ml (range, 0.1-4.2 ng/ml), respectively (P = 0.065). A highly significant correlation was observed between endostatin and VEGF levels among the CCRC patients (r = 0.81, P = 0.0003) but not among controls (r = -0.22, P = 0.37). Endostatin levels are detectable in serum from healthy subjects as well as from CCRC patients. Levels are significantly elevated and correlate with VEGF levels in CCRC patients. Elucidating the nature of this correlation may lend insight into the regulation of tumor angiogenesis in patients with renal cancer.

Adenocarcinoma, Clear Cell↗

[Effect of combined treatment of Shuanghuanglian and recombinant interferon alpha 2a on coxsackievirus B3 replication in vitro].

OBJECTIVE: To investigate the effect of combined treatment of Shanghanglian (SHHL) and recombinant interferon alpha 2a on Coxsackie virus B3 replication. METHODS: Microdose cytopathogenic inhibition effect assay was used in Wish and Vero cultured cells. rIFN-alpha 2a was applied 12 hours before Coxsackievirus B3 inoculation and SHHL was applied 1 hour after Coxsackievirus B3 inoculation. RESULTS: 0.125 mg.ml-1 SHHL has a synergism with rIFN-alpha 2a to inhibit CPE caused by Coxsackievirus B3 on the Wish and Vero cells. The anti-cox-sackievirus activity of combined treatment was 2.58 times higher than that of rIFN-alpha 2a treatment. CONCLUSION: This combined treatment of drugs may be useful in preventing and treating Coxsackie B3 Virus infection.

Antiviral Agents↗

Ovochymase, a Xenopus laevis egg extracellular protease, is translated as part of an unusual polyprotease.

Ovochymase, an extracellular Xenopus laevis egg serine active-site protease with chymotrypsin-like (Phe-X) substrate specificity, is released during egg activation. Molecular cloning results revealed that ovochymase is translated as part of an unusual polyprotein proenzyme. In addition to the ovochymase protease domain at the C terminus of the deduced amino acid sequence, two unrelated serine protease domains were present, each with apparent trypsin-like (Arg/Lys-X) substrate specificity, and thus, they were designated ovotryptase1 (at the N terminus) and ovotryptase2 (a mid domain). Also, a total of five CUB domains were interspersed between the protease domains. The presence of a hydrophobic signal sequence indicated that the polyprotein was secreted. Immunolocalization and Western blot studies of all three proteases showed that they are all present in the perivitelline space of unactivated eggs, apparently as proenzymes processed away from the original polyprotein. Western blot analysis also showed that the vast majority of the proteases in ovary, eggs, and embryos were present as the proenzyme forms, suggesting that the functions of these proteases depend on very limited levels of activation.

Amino Acid Sequence↗

Impact of cytokine administration on the generation of antitumor reactivity in patients with metastatic melanoma receiving a peptide vaccine.

Patients with metastatic melanoma were immunized with an immunodominant peptide derived from the gp100 melanoma-melanocyte differentiation Ag that was modified to increase binding to HLA-A+0201. A total of 10 of 11 patients who received the g209-2M peptide alone developed precursors reactive with the native g209 peptide, compared with only 5 of 16 patients who received g209-2M peptide plus IL-2 (p2 = 0.005). Peptide reactivity closely correlated with the recognition of HLA-A+0201 melanoma cells (p < 0. 001). The decrease in immune reactivity when peptide was administered with IL-2 appeared specific for the immunizing peptide, since reactivity to an influenza peptide resulting from prior exposure was not affected. Preexisting antitumor precursors did not decrease when peptide plus IL-2 was administered. The administration of GM-CSF or IL-12 also resulted in a decrease in circulating precursors compared with the administration of peptide alone, though not as great a decrease as that seen with IL-2. Immunization with peptide plus IL-2 did, however, appear to have clinical impact since 6 of the 16 patients (38%) that received peptide plus IL-2 had objective cancer regressions. It thus appeared possible that immunization with peptide plus IL-2 resulted in sequestering or apoptotic destruction of newly activated immune cells at the tumor site. These represent the first detailed studies of the impact of immunization with tumor peptides in conjunction with a variety of cytokines in patients with metastatic cancer.

Adult↗

High avidity CTLs for two self-antigens demonstrate superior in vitro and in vivo antitumor efficacy.

A majority of the human tumor-associated Ags characterized to date are derived from nonmutated "self"-proteins. Little is currently understood about the nature of the self-reactive lymphocytes that recognize these Ags. We recently characterized two nonmutated tumor-associated Ags for the B16 murine melanoma: tyrosinase-related protein-2 (TRP-2) and the endogenous retroviral envelope protein, p15E. We previously reported that both TRP-2 and p15E reactive CTL could be detected in the spleens of naive animals after a single in vitro stimulation using 10(-5)-10(-6) M of the appropriate Kb-binding 9-amino acid epitope. In this report we show that the CTL found in naive animals are low avidity lymphocytes, that respond only to high concentrations of peptide in vitro. We demonstrate that titration of in vitro-stimulating peptide to limiting concentrations distinguishes qualitative differences in the lymphocyte reactivity to these two Ags between vaccinated and unvaccinated animals. We further demonstrate that in vitro expansion of CTL in either high or low concentrations of stimulating peptide generated CTL cultures with different avidities for the relevant epitopes. CTL expanded in low concentrations demonstrated higher avidity for peptide-pulsed targets and better tumor recognition, when compared to CTL generated in the presence of high concentrations of Ag. More importantly, high avidity CTL demonstrated superior in vivo antitumor activity. These results demonstrate that qualitative differences in the CTL that recognize these two self-Ags are critically important to their in vitro and in vivo anti-tumor efficacy.

Animals↗

Isolation of a Helicobacter pylori protein, FldA, associated with mucosa-associated lymphoid tissue lymphoma of the stomach.

BACKGROUND & AIMS: The growth of gastric mucosa-associated lymphoid tissue lymphoma (MALToma) seems to depend on the stimulation of Helicobacter pylori. We attempted to identify specific antigen(s) from H. pylori strains associated with MALToma. METHODS: Membranous and secreted proteins of H. pylori were compared on sodium dodecyl sulfate-polyacrylamide gel electrophoresis by Western blot using sera from patients with MALToma. RESULTS: A 19-kilodalton protein was seen in all strains isolated from patients with MALToma but uncommonly in other strains. The protein was purified and sequenced. Amino acid sequence comparison showed it was an FldA homologue, a putative flavodoxin protein. DNA sequencing in 26 strains revealed that a nucleotide G insertion at position 481 of the fldA gene was more frequently observed in strains associated with MALToma than other strains (9/9 vs. 6/17; P = 0.002). The mutation caused a short truncation. A recombinant protein with this truncation was expressed and tested. Sera of 12 (70.6%) of 17 patients with MALToma were positive for the antibody to the recombinant protein, and 7 (16.7%) of 42 control patients were positive (12/17 vs. 7/42; P < 0.0001). CONCLUSIONS: Truncated FldA of H. pylori is associated with gastric MALToma. It may be involved in the pathogenesis of gastric MALToma. Antibody to this antigen could be used as a serological marker of the disease.

Adult↗

Interleukin-2 based immunotherapy for metastatic renal cell carcinoma with the kidney in place.

PURPOSE: We assessed morbidity, response and survival in patients with metastatic renal carcinoma treated with high dose intravenous interleukin-2 (IL-2) based immunotherapy with the primary renal tumor in place. MATERIALS AND METHODS: We retrospectively analyzed the records of patients with metastatic renal carcinoma and the primary kidney tumor in situ who were treated at the surgery branch of the National Cancer Institute. Of the patients 607 were treated with IL-2 based therapy. Patient age, sex, sites of extrarenal disease, morbidity, and response and survival rates were examined. RESULTS: From 1986 to 1996, 51 patients with the majority of disease at extrarenal sites were treated with the primary tumor in place. Treatment involved IL-2 based regimens, reflecting the evolution of immunotherapy at the National Institutes of Health. When evaluating only extrarenal sites, response was complete in 1 and partial in 2 of the 51 cases (6%). No responses were noted in the primary renal tumor. Three patients with responses at extrarenal sites underwent nephrectomy. The duration of response in these 3 cases was greater than 88, 11 and 4 months, respectively. Median survival in all 51 patients was 13 months (range 1 to 86). CONCLUSIONS: Select patients may be treated with IL-2 based immunotherapy with the primary renal tumors in place with morbidity. A randomized study is needed to assess the role of cytoreductive nephrectomy for treating metastatic renal cell carcinoma.

Adult↗

Pancreatic tuberculosis with obstructive jaundice--a case report.

Isolated pancreatic tuberculosis (TB) is very rare and its treatment somewhat controversial. We report a case of pancreatic TB diagnosed as pancreatic carcinoma. An 82-yr-old man presented with right upper abdominal pain and obstructive jaundice, without fever or weight loss. Ultrasonography, computed tomography, and endoscopic retrograde cholangiopancreatography showed a mass lesion in the pancreatic head, which caused stricturing of the distal common bile duct and pancreatic duct in the head of the gland. As malignancy was suspected, he underwent a Whipple procedure (pancreaticoduodenectomy). Histological examination of the resection specimen disclosed typical features of tuberculosis in the pancreatic head, lymph nodes, and at the ampulla of Vater. The rest of the abdominal cavity was unremarkable. After receiving antimicrobial therapy for tuberculosis for 6 months, he remains well, without jaundice or a recurrent mass visible by ultrasound.

Aged↗

Prevention of postoperative nausea and vomiting in gynaecological laparotomies: a comparison of tropisetron and ondansetron.

In a randomized, double-blind study, the antiemetic efficacy of a single bolus of tropisetron 5 mg (group T, 37 patients), ondansetron 4 mg (group O, 39 patients) or saline (group C, 45 patients) given at induction was compared in a homogeneous group of 121 patients undergoing gynaecological laparotomy and receiving postoperative patient-controlled intravenous morphine for 24 to 48 hours. Fewer group T and group O patients developed severe nausea compared to group C (P < 0.01, log rank test in Kaplan-Meier analysis). Group T patients also had lower nausea scores than group O at 8 to 16h (P < 0.05). The overall incidences of severe nausea in groups T, O, and C were 5.4%, 17.9%, and 44.4% respectively (P < 0.001, group T vs group C; P < 0.05 group O vs group C). In conclusion, the 5-hydroxytryptamine 3 receptor antagonists tropisetron and ondansetron were superior to placebo in preventing PONV.

Antiemetics↗

Prospective randomized trial of the treatment of patients with metastatic melanoma using chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon alfa-2b.

PURPOSE: The combination of chemotherapy with immunotherapeutic agents such as interleukin-2 and interferon alfa-2b has been reported to provide improved treatment results in patients with metastatic melanoma, compared with the use of chemotherapy alone. We have performed a prospective randomized trial in patients with metastatic melanoma, comparing treatment with chemotherapy to treatment with chemoimmunotherapy. PATIENTS AND METHODS: One hundred two patients with metastatic melanoma were prospectively randomized to receive chemotherapy composed of tamoxifen, cisplatin, and dacarbazine or this same chemotherapy followed by interferon alfa-2b and interleukin-2. Objective responses, survival, and toxicity in the two groups were evaluated at a median potential follow-up of 42 months. RESULTS: In 52 patients randomized to receive chemotherapy, there were 14 objective responses (27%), including four complete responses. In 50 patients randomized to receive chemoimmunotherapy, there were 22 objective responses (44%) (P2 = .071), including three complete responses. In both treatment groups, the duration of partial responses was often short, and there was a trend toward a survival advantage for patients receiving chemotherapy alone (P2 = .052; median survival of 15.8 months compared with 10.7 months). Treatment-related toxicities were greater in patients receiving chemoimmunotherapy. CONCLUSION: With the treatment regimens used in this study, the addition of immunotherapy to combination chemotherapy increased toxicity but did not increase survival. The use of combination chemoimmunotherapy regimens is not recommended in the absence of well-designed, prospective, randomized protocols showing the benefit of this treatment strategy.

Adolescent↗

The significance of pain among Chinese patients with cancer in Hong Kong.

BACKGROUND: The purposes of the survey were to review the significance of pain and its associate factors among Chinese cancer patients in Hong Kong. METHODS: It was a retrospective, cross-sectional survey. One hundred Chinese cancer patients were recruited by convenience from hospices and oncology units in Hong Kong. Data of patients' demographic profile, pain relief measures and pain status were collected by interview. RESULTS: It was found that the presence of current pain among the subjects was 77.0% which was similar to that reported in the United States and United Kingdom. It indicates that the cancer patients in Hong Kong share the same extent of problem as those in the West. This highlights the needs for managing pain as a priority. Unlike the data showed in the West, the pain intensity in the 77% clustered at the lower end of the NRS. Thus, more than three-quarters of the subjects had pain but the majority of them had mild pain. This result is contradictory with the findings in the western countries. It is possible that this discrepancy is caused by a number of factors related to culture, family network support, perceptual processes in abstractions and properties of the tools employed in the assessment of pain intensity. Seventy-six percent of the patients had regular analgesics for their pain. Among them, apart from analgesics, seventeen received massage, three resorted to psychological counseling and four used other pain relief method, e.g. acupuncture. There was also a significant difference as to the types of cancer and the current pain intensity (n = 81, X2 = 15.01, P = 0.04). The differences were demonstrated in liver vs. lung cancers, and liver vs. colorectal cancers (Tukey-HSD test, P < 0.05). Those with lung cancer experienced more pain than those with liver cancer. Similarly, those with liver cancer had more severe pain than those with colorectal cancer. However, there was no association between the presence of metastasis and pain on admission, current pain intensity and pain for the past week. CONCLUSIONS: This survey on the significance of pain demonstrates the extent of the problem in Chinese cancer patients in Hong Kong. It highlights the priority of need in cancer pain management.

Aged↗

The construction of a pain intensity verbal rating scale in Chinese.

BACKGROUND: Despite the growing interest of developing multidimensional scales, the use of unidimensional scales in assessing clinical pain is popular for its simplicity, efficiency and ease of administration. The purposes of this study were: first, to explore the pain intensity descriptors used among Chinese. Second, it was to construct a verbal rating scale for pain assessment. METHODS: It consisted of two stages. Stage One was a cross-sectional descriptive survey to explore the pain intensity descriptors used among adult Chinese in Hong Kong. Stage Two was a Q-sorting technique to array the pain intensity descriptors obtained in Stage One. This was to construct a verbal rating scale (VRS) for pain assessment. RESULTS: Nine hundred and eighty six healthy Chinese adults participated in Stage One. The ten pain intensity descriptors obtained were bearable ([symbol: see text]), crushing the heart and lungs ([symbol: see text]), crucifying pain ([symbol: see text]), excruciating pain ([symbol: see text]), indescribable ([symbol: see text]), quite painful ([symbol: see text]), painful ([symbol: see text]), slight pain ([symbol: see text]), unbearable ([symbol: see text]) and very painful ([symbol: see text]). In Stage Two, fifty-four baccalaureate-nursing students participated in the Q-sorting procedure. They were asked to rank the pain intensity descriptors according to a set of psychometric criteria. A vertical VRS was constructed with the least pain at the bottom and the most pain on the top. A 'no pain' was added to the bottom of the scale. CONCLUSIONS: The order of the rank was no pain, slight pain, quite painful, painful, very painful, bearable, indescribable, excruciating pain, unbearable, crushing the heart and lungs and crucifying pain. It is anticipated that a VRS of this kind has its value in the measurement of pain intensity with cultural relevancy.

Adult↗

The role of gastric acid and Helicobacter pylori in the natural course of duodenal ulcer.

This study was conducted using roxatidine acetate or Mylanta combined with metronidazole and amoxicillin to evaluate the role of acid and Helicobacter pylori in the natural course of the duodenal ulcer. Eighty-three patients with H. pylori positive duodenal ulcers were randomly allocated into one of four treatment groups. Group A: roxatidine 75 mg hs for 8 weeks; Group B: the same as group A + metronidazole 250 mg and amoxicillin 250 mg qid for 1 week on the 3rd week; Group C: Mylanta (combined hydroxide of magnesium and aluminum) 20 ml qid for 8 weeks; Group D: the same as group C + metronidazole 250 mg and amoxicillin 250 mg qid for 1 week on the 3rd week. Repeated endoscopies were performed on the 8th week post the initial treatment and the sixth and 12th month post the termination of treatment, or, at the earliest recurrence of symptoms. Eradication of H. pylori was considered to be successful if the culture, histology and CLO test all showed negative. The ulcer healing rates of Groups A, B, C and D were 95%, 100%, 61% and 86%, respectively, with a significant difference between A and C. The eradication rates of groups B and D were 81% and 62%, respectively, without any significant difference. The 12 months cumulative ulcer recurrence rates were 72%, 15%, 80% and 22%, respectively, with a significant difference between each paired groups with and without antibiotics. In conclusions, roxatidine is effective in the healing of duodenal ulcer. One-week roxatidine-based triple therapy is powerful in the eradication of H. pylori. Potent acid suppression is sufficient to heal the duodenal ulcer. Eradication of H. pylori can potentiate ulcer healing under insufficient acid suppression. A causal role for H. pylori in recurrent duodenal ulcer is strongly supported by a much lower recurrence of ulcer in H. pylori free patients.

Adolescent↗

A multicenter study on eradication of Helicobacter pylori infection in patients with duodenal ulcer by lansoprazole-antibiotics combined therapy.

The aim of this prospective randomized multicenter study was to find out if there is one or several promising regimens containing lansoprazole with various combinations of antibiotics which have a high eradication rate of Helicobacter pylori, few side-effects, good patient compliance, and relative low cost if possible. Two hundred and ninety-seven patients with H. pylori positive duodenal ulcer were enrolled and randomly allocated into one of the five treatment groups: 1) group A: received lansoprazole 30 mg once daily for 2 weeks plus amoxicillin (AM) 500 mg and metronidazole (MZ) 500 mg twice daily for one week in the first week; 2) group B: the AM in group A was replaced by clarithromycin (CM) 250 mg; 3) group C: the MZ in group A was replaced by CM 250 mg; 4) group D: the AM and CM in group C was used for 2 wk; 5) group E: the CM in group D was doubled to 500 mg twice daily. All patients received endoscopies pre- and 4-6 weeks post termination of treatment. H. pylori was detected by culture, histology and rapid urease test (CLO test). 13C-urea breath test was performed if the patients refused the second endoscopy. The E-test was adopted to evaluate the MZ and CM resistance of H. pylori. Totally, 253 patients completed the study. The eradication rate of groups A, B, C, D and E were 75%, 80%, 78%, 92%, and 96%, respectively. The eradication rate of group E was significantly higher than that of groups A, B, or C. There were no significant differences of eradication rates between the groups D and E. Sixty-seven cases (28.8%) were MZ-resistant. The difference of eradication rates between MZ-S and MZ-R patients was significant in group A (85.3% vs. 42.9%) and in the combination of groups A and B (83.8% vs. 59.4%). Good compliance (defined as taking > 90% of medications) was seen in more than 90% of cases in each group. Triple therapy containing lansoprazole 30 mg once daily, AM 500 mg and CM 250 mg twice daily for two weeks is a promising regimen which reaches a high eradication rate, avoids MZ resistance, and has very good patient compliance at an acceptable cost.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens.

BACKGROUND: The characterization of the genes encoding melanoma-associated antigens MART-1 or gp100, recognized by T cells, has opened new possibilities for the development of immunization strategies for patients with metastatic melanoma. With the use of recombinant adenoviruses expressing either MART-1 or gp100 to immunize patients with metastatic melanoma, we evaluated the safety, immunologic, and potential therapeutic aspects of these immunizations. METHODS: In phase I studies, 54 patients received escalating doses (between 10(7) and 10(11) plaque-forming units) of recombinant adenovirus encoding either MART-1 or gp100 melanoma antigen administered either alone or followed by the administration of interleukin 2 (IL-2). The immunologic impact of these immunizations on the development of cellular and antibody reactivity was assayed. RESULTS: Recombinant adenoviruses expressing MART-1 or gp100 were safely administered. One of 16 patients with metastatic melanoma receiving the recombinant adenovirus MART-1 alone experienced a complete response. Other patients achieved objective responses, but they had received IL-2 along with an adenovirus, and their responses could be attributed to the cytokine. Immunologic assays showed no consistent immunization to the MART-1 or gp100 transgenes expressed by the recombinant adenoviruses. High levels of neutralizing antibody were found in the pretreatment sera of the patients. CONCLUSIONS: High doses of recombinant adenoviruses could be safely administered to cancer patients. High levels of neutralizing antibody present in patients' sera prior to treatment may have impaired the ability of these viruses to immunize patients against melanoma antigens.

Adenoviridae↗

dATP causes specific release of cytochrome C from mitochondria.

The induction of the Mitochondrial Permeability Transition (MPT) has recently been associated with the release of apoptogenic cytochrome c, which could come about in a swelling-dependent or swelling-independent manner. We observed that canonical inducers of MPT (Ca2+, t-butyl hydroperoxide, atractyloside) induce a swelling-dependent release of cytochrome c, and that osmotic support of mitochondria with PEG-1000 abolishes mitochondrial swelling, protein release, and cytochrome c release by these inducers. By contrast, it was observed that dATP is a potent inducer that caused release of cytochrome c in a swelling independent manner, i.e. even in the presence of osmotic support by PEG-1000; in addition this release of cytochrome c is inhibitable by cyclosporin A. The dATP-dependent and swelling-independent release of cytochrome c from mitochondria is not inhibitable by the protease inhibitor z-VAD, suggesting that it is not mediated by upstream caspases. This is the first report to our knowledge that a chemical compound may directly cause release of cytochrome c from mitochondria, and could explain the toxicity of dATP in the context of the genetic immunodeficiency diseases Adenosine Deaminase deficiency and Purine Nucleotide Phosphorylase deficiency.

Adenosine Triphosphate↗

Sintering and oxidation using a novel ultrahigh vacuum transmission electron microscope with in situ magnetron sputtering.

The synthesis and processing of materials is often highly sensitive to the presence of trace contaminants and a number of technologically important materials demand the clean conditions associated with an ultrahigh vacuum environment. With increasing interest in understanding materials phenomena occurring on smaller and smaller length scales, the transmission electron microscope is finding increasing application in the characterization of new materials and processes. The need for ex situ sample preparation prior to analysis can raise questions regarding the validity of the data, however, due to contamination and the introduction of microstructural artifacts. In this paper we discuss the application of the ultrahigh vacuum transmission electron microscope to in situ studies of materials synthesis. To illustrate the capabilities of the electron microscope in this context, we present two case studies: the synthesis and subsequent sintering of supported copper nanoparticles, and the initial stages of the growth of Cu2O on clean (001) Cu. We describe the novel aspects of the instrumentation used, the methods of sample preparation, and our application of the plan-view imaging technique to in situ investigations.

Copper↗