Search PubMed⌕ Search

Biomedical subjects

S Shen

Publications and source records attributed to S Shen.

At least 109 records · Page 6Linked to original sources
PubMed1999

A clinical trial of radioimmunotherapy with 67Cu-2IT-BAT-Lym-1 for non-Hodgkin's lymphoma.

UNLABELLED: Encouraged by the results of 131I-Lym-1 therapy trials for patients with B-cell non-Hodgkin's lymphoma (NHL), this phase I/II clinical trial of 67Cu-2IT-BAT-Lym-1 was conducted in an effort to further improve the therapeutic index of Lym-1-based radioimmunotherapy. Lym-1 is a mouse monoclonal antibody that preferentially targets malignant lymphocytes. 67Cu has beta emissions comparable to those of 131I but has gamma emissions more favorable for imaging. The macrocyclic chelating agent 1,4,7,11-tetraazacyclotetradecane-N,N',N",N"'-tetraacetic acid binds 67Cu tightly to form a stable radioimmunoconjugate in vivo. METHODS: All 12 patients had stage III or IV NHL that had not responded to standard therapy; 11 had intermediate- or high-grade NHL. At 4-wk intervals, patients received up to four doses of 67Cu-2IT-BAT-Lym-1, 0.93 or 1.85-2.22 GBq/m2 (25 or 50-60 mCi/m2), with the lower dose used when NHL was detected in the bone marrow. RESULTS: 67Cu-2IT-BAT-Lym-1 provided good imaging of NHL and favorable radiation dosimetry. The mean radiation ratios of tumor to body and tumor to marrow were 28:1 and 15:1, respectively. Tumor-to-lung, -kidney and -liver radiation dose ratios were 7.4:1, 5.3:1 and 2.6: 1, respectively. This 67Cu-2IT-BAT-Lym-1 trial for patients with chemotherapy-resistant NHL had a response rate of 58% (7/12). No significant nonhematologic toxicity was observed. Hematologic toxicity, especially thrombocytopenia, was dose limiting. CONCLUSION: 67Cu remains an option for future clinical trials. This study established 67Cu-2IT-BAT-Lym-1 as a safe, effective treatment for patients with NHL.

Bone Marrow↗
PubMed1999

Practical determination of patient-specific marrow dose using radioactivity concentration in blood and body.

UNLABELLED: Accurate determination of red marrow radiation is important because myelotoxicity is often dose limiting in radioimmunotherapy. The S-value methodology assumes a fixed red marrow mass as defined by the standard Medical Internal Radiation Dose (MIRD) mathematic phantom. Substantial error can be introduced in marrow radiation estimates because red marrow mass varies from patient to patient. In this work we describe a patient-specific marrow dosimetry methodology that does not require an explicit estimate of marrow mass. METHODS: Photon radiation to marrow from all sources can be considered as the total body to marrow. Based on photon radiation from body and electron radiation from blood, a patient-specific marrow dose can be determined by counting blood and total body radioactivity and measuring body weight. RESULTS: The deviation in marrow dose calculation using total body to represent all photon radiation was 3.9% in 66 patients administered 131I-labeled antibodies and was 9.1% in 18 patients administered 67Cu-labeled antibodies. The differences between this patient-specific approach and estimates based on standard anatomy were considerable, ranging from -35% to 88%. The differences were greater when patients' weights differed substantially from the MIRD reference man phantom. CONCLUSION: For radiopharmaceuticals that do not bind marrow, patient-specific marrow dosimetry can be independent of the actual marrow mass of a patient. Patient-specific marrow dosimetry can be determined using radioactivity concentration in blood and body.

Body Weight↗
PubMed1999

[Perioperative use of peripherally inserted central catheter for parenteral nutrition in patients with abdominal malignancy].

OBJECTIVE: To evaluate the use of peripherally inserted central catheter(PICC) in perioperative patients with abdominal malignancies for parenteral nutrition. METHODS: PICC was performed in 33 patients while subclavicular vein insertion in 30 patients for comparison in order to analyse prospectively the advantages and disadvanges of PICC. RESULTS: There was no difference in the rate of success of catheter placement and infection between PICC and the "subclavicular" insertion (P > 0.05), but PICC had significantly longer indwelling time than that of the "subclavicular" insertion (P < 0.05). There were less risks associated with PICC insertions, but the flow rate of was lower(p < 0.05). CONCLUSIONS: PICC can be widely used on account of its longer indwelling time, easy and safe insertion.

Abdominal Neoplasms↗
PubMed1998

Cyclic AMP elevation is sufficient to promote the survival of spinal motor neurons in vitro.

The short-term survival of highly purified embryonic spinal motor neurons (SMNs) in culture can be promoted by many peptide trophic factors, including brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), fibroblast growth factor (FGF), glial-derived neurotrophic factor (GDNF), and hepatocyte growth factor (HGF). We have asked whether these peptides are sufficient to promote the long-term survival of purified E15 SMNs. Contrary to previous reports, we find that when SMNs are cultured in serum-free medium containing a single peptide trophic factor only approximately one-third of the cells survive for 3 d in culture. When multiple factors are combined, additive effects on survival are observed transiently, but by 7 d of culture the majority of SMNs has died. Surprisingly, when cAMP levels are elevated, the majority of SMNs extend processes and survive for 1 week in culture in the absence of peptide trophic factors, even in low-density cultures. A combination of five peptide trophic factors, together with cAMP elevation, promotes the long-term survival of most of the SMNs in serum-free culture for 3 weeks. These findings provide useful culture conditions for studying the properties of SMNs and have implications for the treatment of motor neuron diseases.

1-Methyl-3-isobutylxanthine↗
PubMed1998

A strong nitrogen source-regulated promoter for controlled expression of foreign genes in the yeast Pichia pastoris.

In methylotrophic yeasts, glutathione-dependent formaldehyde dehydrogenase (FLD) is a key enzyme required for the metabolism of methanol as a carbon source and certain alkylated amines such as methylamine as nitrogen sources. We describe the isolation and characterization of the FLD1 gene from the yeast Pichia pastoris. The gene contains a single short intron with typical yeast-splicing signals near its 5' end, the first intron to be demonstrated in this yeast. The predicted FLD1 product (Fld1p) is a protein of 379 amino acids (approx. 40 kDa) with 71% identity to the FLD protein sequence from the n-alkane-assimilating yeast Candida maltosa and 61-65% identity with dehydrogenase class III enzymes from humans and other higher eukaryotes. Using beta-lactamase as a reporter, we show that the FLD1 promoter (PFLD1) is strongly and independently induced by either methanol as sole carbon source (with ammonium sulfate as nitrogen source) or methylamine as sole nitrogen source (with glucose as carbon source). Furthermore, with either methanol or methylamine induction, levels of beta-lactamase produced under control of PFLD1 are comparable to those obtained with the commonly used alcohol oxidase I gene promoter (PAOX1). Thus, PFLD1 is an attractive alternative to PAOX1 for expression of foreign genes in P. pastoris, allowing the investigator a choice of carbon (methanol) or nitrogen source (methylamine) regulation with the same expression strain.

Alcohol Oxidoreductases↗
PubMed1998

Proteolytic mapping of the coronavirus infectious bronchitis virus 1b polyprotein: evidence for the presence of four cleavage sites of the 3C-like proteinase and identification of two novel cleavage products.

We have previously reported that the 3C-like proteinase of the coronavirus infectious bronchitis virus (IBV) is responsible for processing of the 1a and 1a/1b polyproteins to three mature products of 24, 10, and 100 kDa (Liu et al., 1994, 1997; Ng and Liu, 1998). The C-terminal cleavage site of the 100-kDa protein was defined to be the Q891(1b)-S892(1b) dipeptide bond encoded by nucleotides 15,129 to 15,134 (Liu and Brown, 1995). In this report, other cleavage sites of the 3C-like proteinase in the polyprotein encoded by the ORF 1b region were mapped by coexpression, deletion, and site-directed mutagenesis studies. Using two ORF 1b-specific antisera, V58 and V17, three more Q-S(G) dipeptide bonds, encoded by nucleotides 16,929 to 16,934, 18,492 to 18,497, and 19,506 to 19,511, respectively, were demonstrated to be the cleavage sites of the 3C-like proteinase. Cleavage at these four positions would result in the release of four mature products with molecular masses of approximately 68, 58, 39, and 35 kDa. Among them, the 39- and 35-kDa proteins were specifically identified in IBV-infected cells. Taken together with the 100-kDa protein previously identified, these results suggest that the ORF 1b region of IBV mRNA1 may be able to encode five mature products.

Animals↗
PubMed1998

Proteolytic processing of the polyprotein encoded by ORF1b of the coronavirus infectious bronchitis virus (IBV).

We present here evidence demonstrating that four previously predicted Q-S(G) cleavage sites, encoded by the IBV sequences from nucleotide 15,129 to 15,134, 16,929 to 16,934, 18,492 to 18,497, and 19,506 to 19,511, respectively, can be recognised and transcleaved by the 3C-like proteinase. Five mature products with sizes of approximately 100 kDa, 65 kDa, 63 kDa, 42 kDa and 35 kDa are released from the ORF1b polyprotein by the 3C-like proteinase-mediated cleavage at these positions. Meanwhile, expression of plasmids containing only the ORF1b region showed no autocleavage of the polyprotein encoded, suggesting that the 3C-like proteinase may be the sole proteinase involved in processing of the 1b polyprotein. These data may therefore represent a complete processing map of the polyprotein encoded by ORF1b of mRNA1.

Antibodies↗
PubMed1998

Quantification of iodine-131 in tumors using a threshold based on image contrast.

Accurate and reproducible quantification of tumor radioactivity by imaging requires definition of a region of interest (ROI) for the tumor. The use of a threshold for creating the tumor ROI based on tumor-to-background image contrast (image contrast) was examined. Quantification of iodine-131 in spheres in a phantom that simulated tumors in patients was investigated using planar imaging and geometric-mean and effective-point-source methods. Thresholds that provided the least quantitative error for spheres with different diameters (1-5 cm) and locations (0-11 cm deep in the body), 131I concentrations (0.037-3.2 MBq/ml), and sphere-to-background concentration ratios (1:0, 14:1 and 7:1) were investigated. The correlation between threshold and sphere image contrast was examined. The phantom study showed that an appropriate threshold value for quantification of tumor radioactivity could be determined using image contrast for a single view, provided that image contrast was >/=1.5. The error of quantification was less than 10% for spheres with high image contrast (>/=1.5) but was greater than 17% for spheres with low image contrast (<1.5). When image contrast-dependent thresholds were applied to patient studies, 131I concentrations determined by imaging were in good agreement with the concentrations determined by counting biopsy samples. Additionally, reproducibility was improved when compared with a visual boundary method. It is concluded that accurate and reproducible quantification of radioactivity in tumors is achievable using thresholds based on image contrast if image contrast is greater than or equal to 1.5. Optimal thresholds for quantification of tumor radioactivity were similar if image contrast was similar despite differing tumor diameters, locations and 131I concentrations. Under certain circumstances, the effective-point-source method was preferable to the geometric-mean method.

Humans↗
PubMed1998

Prolonged survival associated with immune response in a patient treated with Lym-1 mouse monoclonal antibody.

A patient with aggressive, chemotherapy-resistant non-Hodgkins lymphoma (NHL) was treated with 131I-Lym-1, a mouse antibody, on a protocol designed for serial therapy. Human anti-mouse antibody (HAMA) developed within 1 month of initial therapy. The patient also developed an antibody to the hypervariable region of the Lym-1 antibody (Lym-1 specific). Because the patient was responding to therapy, plasmaphoresis was used to reduce the level of HAMA followed by unlabeled Lym-1 calculated to be sufficient to block residual HAMA. This allowed additional therapy on three subsequent occasions over 5 months. Despite very high HAMA levels, no untoward effects from administrations of Lym-1 were observed. The HAMA response of the patient included anti-Lym-1 specific antibodies containing anti-idiotypic antibodies. The anti-Lym-1 antibody level has been sustained over the 9 year interval since 131I-Lym-1 therapy and has been associated with a uniquely long remission of the patient's disease. These observations demonstrate that, under certain circumstances, radioimmunotherapy (RIT) can be given safely and effectively despite HAMA. Anti-idiotypic antibodies could have induced an immune cascade that contributed to the prolonged disease-free survival of the patient.

Animals↗
PubMed1998

Low-dose, fractionated radioimmunotherapy for B-cell malignancies using 131I-Lym-1 antibody.

PURPOSE: This trial was conducted to assess the toxicity and efficacy of 131I-Lym-1 in patients with either malignant B-cell non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL) using low-dose, fractionated radioimmunotherapy (RIT). MATERIALS AND METHODS: Thirty adult patients who had advanced B-cell malignancies (25 NHL and 5 CLL) had progressed despite standard therapy; 12 patients entered the trial with Karnofsky performance status (KPS) of equal to or greater than 60. Patients were treated with a series of intravenous doses of 131I-Lym-1 with a goal of reaching a cumulative dose in each patient of at least 300 mCi. All patients were Lym-1 reactive. Clinical responses and immediate toxicity were evaluable in all 30 patients and delayed toxicity in 26. RESULTS: Toxicity to Lym-1 antibody occurred with 28% of the 176 doses and was transient. Human antimouse antibodies (HAMA) were generated in 30% after a mean of 4 doses, but interrupted therapy in only 10% of the patients. Thrombocytopenia was dose-limiting; there were no deaths due to toxicity. Tumor regression occurred in 25 (83%) of the patients and was great enough, and durable enough, in 17 (57%) to qualify them as responders; 13 NHL patients and 4 CLL patients. Advanced disease often interrupted therapy prematurely. However, 18 patients received at least 180 mCi of 131I-Lym-1; 17 (94%) of these responded to the therapy. CONCLUSION: Although advanced disease often interrupted therapy prematurely, the results from 131I-Lym-1 therapy are clearly promising and warrant additional trials.

Adult↗
PubMed1998

Maximum-tolerated dose, toxicity, and efficacy of (131)I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin's lymphoma.

PURPOSE: Lym-1, a monoclonal antibody that preferentially targets malignant lymphocytes, has induced remissions in patients with non-Hodgkin's lymphoma (NHL) when labeled with iodine 131 ((131)I). Based on the strategy of fractionating the total dose, this study was designed to define the maximum-tolerated dose (MTD) and efficacy of the first two, of a maximum of four, doses of (131)I-Lym-1 given 4 weeks apart. Additionally, toxicity and radiation dosimetry were assessed. MATERIALS AND METHODS: Twenty patients with advanced NHL entered the study a total of 21 times. Thirteen (62%) of the 21 entries had diffuse large-cell histologies. All patients had disease resistant to standard therapy and had received a mean of four chemotherapy regimens. (131)I-Lym-1 was given after Lym-1 and (131)I was escalated in cohorts of patients from 40 to 100 mCi (1.5 to 3.7 GBq)/m2 body surface area. RESULTS: Mean radiation dose to the bone marrow from body and blood (131)I was 0.34 (range, 0. 1 6 to 0.63) rad/mCi (0.09 mGy/MBq; range, 0.04 to 0.17 mGy/ MBq). Dose-limiting toxicity was grade 3 to 4 thrombocytopenia with an MTD of 100 mCi/m2 (3.7 GBq/m2) for each of the first two doses of (131)I-Lym-1 given 4 weeks apart. Nonhematologic toxicities did not exceed grade 2 except for one instance of grade 3 hypotension. Ten (71 %) of 14 entries who received at least two doses of (131)I-Lym-1 therapy and 11 (52%) of 21 total entries responded. Seven of the responses were complete, with a mean duration of 14 months. All three entries in the 100 mCi/m2 (3.7 MBq/m2) cohort had complete remissions (CRs). All responders had at least a partial remission (PR) after the first therapy dose of (131)I-Lym-1. CONCLUSION: (131)I-Lym-1 induced durable remissions in patients with NHL resistant to chemotherapy and was associated with acceptable toxicity. The nonmyeloablative MTD for each of the first two doses of (131)I-Lym-1 was 100 mCi/m2 (total, 200 mCi/m2) (3.7 GBq/m2; total, 7.4 GBq/m2).

Adult↗
PubMed1998

[Expression of connexin genes in the liver of different stages of embryo development].

To explore the relationship between the connexin (Cx) gene expression and cellular differentiation in the liver of different embryonic stage, we studied the expression of Cx genes in the liver of different embryonic ages by Northern blot hybridization technique, using the series of Cx gene as the molecular probes. The expression of Cx genes exhibited organ specificity, Cx26, Cx32, and Cx43 were expressed in the liver while others had no signal. Cx26, Cx32, and Cx43 genes exhibited different expression models in different developmental stages of the fetus. Cx43 did not express in human liver after birth, but it expressed in the fetal stage. The results suggest that the expression of Cx genes plays an important role in the organ development and may be a key gene to regulate some differentiational events associated with cell growth and organ development.

Cell Differentiation↗
PubMed1998

[The rescue of iodine allergy by contrast enhanced CT].

We summarized 51 cases of iodine allergy and allergic shock induced by contract-enhanced computed tomography (CT). It is suggested that (1) the appropriate measures must be taken to prevent the side effects of ionic contrast medium; (2) a set of first-aid drug and essential equipment must be prepared; (3) the staff of CT room must be trained with the first-aid techniques and knowledge.

Adolescent↗
PubMed1998

[The role of diet consultation on improvement of the diet nutrition in pregnant women].

OBJECTIVE: To study the improvement of the intakes of various nutrients including protein, fat, carbohydrate, fibers, calcium, iron, zinc et al, in pregnant women after appropriate diet consultation by doctors. METHODS: 100 cases of pregnant women coming to our diet consultation clinic were randomly selected, in which 50 cases (control group) came for the first time and another 50 cases (study group) were for the third visit at least. The diet nutrition of the study group after the second consultation were compared with that before consultation and with concurrent control group. RESULTS: After diet consultation, except for retinol, the intake of various nutrients, including calorie intake, protein, fibers, magnesium, calcium, phosphorus, iron, zinc, vitamin E, riboflavin, thiamine, nicotinic acid, in study group were significantly improved compared with that of the study group before diet consultation and of the control group (P < 0.01). CONCLUSION: Diet consultation plays excellent role in promoting scientific and appropriate nutrients intake of pregnant women.

Adult↗
PubMed1998

[Clinical applications of computer system for diet consultation of pregnant women].

OBJECTIVE: To investigate nutritional status of women in different gestational ages and seasons and the role of diet consultation by a computer system on the improvement of intakes of nutrients of pregnant women. METHODS: 712 women in different gestational ages and 747 cases in different seasons received diet consultation by the computer system. A comparison was done for nutritional status between pregnant women with consultation and the women without consultation. RESULTS: Major pregnant women in various gestational ages and seasons was deficient in nutrient intake. However, the nutritional status was significantly improved in women following diet consultation in comparison with the women not received diet consultation. CONCLUSION: Computer system really plays an excellent role in promoting diet consultation and improvement of diet condition of pregnant women.

Diet Surveys↗