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Biomedical subjects

S He

Publications and source records attributed to S He.

At least 19 recordsLinked to original sources
PubMed1992

Use of radiation with or without WR-2721 in advanced rectal cancer.

One hundred patients with inoperable, unresectable, or recurrent adenocarcinoma of the rectum were stratified and randomized to WR-2721 plus radiation therapy (WR + RT) or radiation therapy (RT) only treatment arms. The protector, WR-2721, was administered at a dose of 340 mg/m2 15 minutes before RT, 4 days a week for 5 weeks. The entire pelvis received 225 cGy per fraction for a total of 4500 cGy. The RT only group received the same treatment schedule. After this, both groups received a conedown of 720 cGy in 4 fractions. Inoperable and unresectable cases received a second conedown of 720 cGy. No moderate or severe pelvic normal tissue late effects were seen in the 34 evaluable patients in the combination group. However, in the RT only group, 5 of 37 evaluable patients exhibited late effects of moderate or severe degree. This difference was statistically significant (P = 0.03). There was no evidence of tumor protection by WR-2721. Sixteen percent of patients randomized to the WR + RT group had a complete response compared with 10% in the RT only group. The conditions of 12 patients of 100 became operable and 8 were resected. Seven of these patients remain free of recurrence.

Adult↗
PubMed1992

Antibody drug carrier for immunotherapy of superficial bladder cancer: ultrastructural studies.

Superficial bladder cancer represents a promising target for intravesical, antibody-guided therapy. The construction of an optimum antibody-cytotoxic drug conjugate depends mostly on the appropriate selection of a monoclonal antibody (mAb). We have used immunogold labeling and SEM to specifically map the distribution of antigens expressed on three bladder cancer cell lines and on the luminal surface of biopsies from human transitional cell carcinoma of various grades and from normal bladder mucosa. The 48-127 mAb, which recognizes a M(r) 54,000 surface glycoprotein (gp54), was found to be very promising as a potential drug carrier. This antibody reacts with the surface of cells from low- and high-grade tumors; it does not react with the normal urothelium. Labeling of normal bladder mucosa was observed, however, on microvillous intermediate urothelial cells occasionally exposed by small areas of desquamation. The 48-127 mAb could target drugs to all areas of transformed urothelium while avoiding drug delivery to the normal, undesquamated bladder mucosa. Kinetics of gp54/48-127/gold complexes were tested in vitro with T24 and RT4 human bladder carcinoma cell lines incubated in the presence of the 48-127 mAb directly conjugated with 17.7-nm gold particles. Internalization of the gp54/48-127/gold complex was readily demonstrated by transmission electron microscopy. These results suggest that the 48-127 mAb represents a valuable drug carrier for intravesical therapy, allowing specific tumor targeting and internalization of various cytotoxic agents.

Aged↗
PubMed1992

Interim analysis of a randomized trial of radiation therapy of rectal cancer with/without WR-2721.

The objectives of this randomized trial are to define the maximum tolerated dose of radiation therapy, at curative dose levels, that can be delivered following WR-2721, and to observe the anti-tumor effects and normal tissue responses. One hundred patients with inoperable, unresectable, or recurrent rectal cancer were stratified and randomized to radiation only, or WR-2721 and radiation. The entire pelvis is treated with 4 portals 4 times a week to a total of 4500 cGy (first level dose) in 5 weeks. WR-2721, 340 mg/m2 was given 15 minutes before radiation to the combination group. Subsequently, both groups received a conedown of 720 cGy in 4 days to 144(2) cm portals APPA, and if originally inoperable or unresectable 720 cGy in four days to second conedown of 64(2) cm. Patients were observed from 3 to 18 months (median = 12 months). No significant hypotension or hematologic toxicity occurred in the WR-2721 treated group. Mild to moderate emesis occurred in 80% of the courses. (No antiemetics were used.) Moderate or severe acute toxicities to normal tissues were observed less frequently in the WR-2721 arm. No moderate or severe late toxicities to the skin, mucous membrane, urinary bladder or intestine was observed in the WR-2721 group, however, 5 patients treated with radiation alone experienced moderate or severe late toxicity to these organs. No evidence of tumor protection was observed.

Adenocarcinoma↗
PubMed1992

Tumorigenicity of cyclopenta[a]phenanthrene derivatives and micronucleus induction in mouse skin.

The most potent carcinogen of the cyclopenta[a]phenanthrene series, 15, 16-dihydro-11-methylcyclopenta[a]phenanthren-17-one and its non-carcinogenic, unmethylated parent compound, were compared for their abilities to induce micronuclei in epidermal keratinocytes after application onto the dorsal skin of Skh/HR-1 hairless mice. Although both substances were shown to be mutagenic in vitro, only the 11-methyl derivative has been proven to initiate cancer in TO and Sencar mouse strains. In the present study, only the 11-methyl derivative was active as a cancer initiator in Skh/HR-1 mice. For studying micronucleus induction, a preliminary experiment was conducted to establish doses of both chemicals that allowed cell survival. Subsequently, micronucleus induction in epidermal keratinocytes was shown to agree with the cancer-initiating potential of the two compounds. Only the carcinogenic derivative induced a statistically significant increase in micronuclei, over the range 10-100 nmol. This is considerably lower than the dose of approximately 1600 nmol commonly used to initiate skin cancer in mice, but is comparable to the active dose range for skin micronucleus induction by benzo[a]pyrene, a chemical of equivalent carcinogenic potency.

Animals↗
PubMed1992

[Hepatic segmentectomy using microwave tissue coagulator].

Hepatic segmentectomy using a microwave tissue coagulator guided by intraoperative ultrasonography is a new operative procedure, which our research unit was the first to start using from 1990. Up to now we have performed this kind of operation with success in 26 cases. Our results suggested that the new procedure simplified the original operation and greatly reduced the risk of hemorrhage and iatrogenic spread of the cancer cells during operation. Besides, this operation as a kind of definite anatomic hepatectomy can minimally resect the tumor bearing tissue in a radical fashion, while maximally preserve the tumor-free tissue of the liver.

Adult↗
PubMed1992

An outbreak of poisoning from Penicillium cyclopium contaminated dried persimmon.

It is the first report of an outbreak of 114 food-poisoning cases due to consumption of Penicillium cyclopium contaminated dried persimmon. Gastralgia, diarrhea, dizziness and general malaise are chief symptoms of the poisoning, with incubation period of 2-6 hrs generally and a short disease period (generally recovered within 2-3 days). No enteropathogenic organism, pathogenic coccus and Campylobacter jejuni were detected. Surface fungi counts were 49,000/g, 21.3 times of that discovered in the marketed dried persimmon. Penicillium cyclopium Westling was the dominant fungus isolated. Mouse toxicity tests were carried out with the crude extracts of the fungus culture. Diarrhea, tremor and convulsion were observed before death. During autopsy, necrosis and hemorrhagic foci were observed in G.I. tract after intra-peritoneal injection and intubation. In histo-pathological examination, different degree of necrosis and scaling of gastro-intestinal mucous membrane, lymphocyte infiltration, and necrosis of liver cells and renal tubule epithelial cells could be seen.

Adolescent↗
PubMed1991

The surface-exposed tyrosine residue Tyr83 of pea plastocyanin is involved in both binding and electron transfer reactions with cytochrome f.

Site-directed mutants of the pea plastocyanin gene in which the codon for the surface-exposed Tyr83 has been changed to codons for Phe83 and Leu83 have been expressed in transgenic tobacco plants. The mutant proteins have been purified to homogeneity and their conformations shown not to differ significantly from the wild-type plastocyanin by 1H-NMR and CD. Overall rate constants for electron transfer (k2) from cytochrome f to plastocyanin have been measured by stopped-flow spectrophotometry and rate constants for binding (ka) and association constants (KA) have been measured from the enhanced Soret absorption of cytochrome f on binding plastocyanin. These measurements allow the calculation of the intrinsic rate of electron transfer in the binary complex. An 8-fold decrease in the overall rate of electron transfer to the Phe83 mutant is due entirely to a decreased association constant for cytochrome f, whereas the 40-fold decrease in the overall rate of electron transfer to the Leu83 mutant is due to weaker binding and a lower intrinsic rate of electron transfer. This indicates that Tyr83 is involved in binding to cytochrome f and forms part of the main route of electron transfer.

Base Sequence↗
PubMed1991

Micronuclei induction by dichlorvos in the mouse skin.

Micronucleus (MN) induction in cultured keratinocytes was investigated following skin painting of HRA/Skh mice with the pesticide, dichlorvos. Whole skin and partially-purified epidermal cells from 5-6 week old male animals were cultured for 4 days in vitro after single topical applications of various concentrations of dichlorvos in vivo. Appropriate doses, allowing optimum survival of keratinocytes, were selected following an initial range-finding experiment. To evaluate MN induction in dividing cells, the cytokinesis-block method was employed. Results showed statistically significant MN at all dose levels in partially-purified epidermal cells and a positive trend with respect to dose from 51 to 1033 nmol dichlorvos. A significant increase in MN was also detectable in cultured cells from whole skin, dissociated within as little as 1 h after application of dichlorvos. Although a number of technical difficulties are associated with the skin micronucleus method, it has been used successfully in this laboratory to detect several skin carcinogens of both high and low potency. Since dichlorvos is rapidly absorbed through the skin, and can induce MN in skin cells of treated mice, this compound may therefore be considered to pose a contact hazard for exposed humans.

Administration, Topical↗
PubMed1990

[The construction of shuttle plasmid vector of Streptomyces and E. coli].

A shuttle plasmid vector, pSE-3 was constructed using the Streptomyces plasmid pIJ486 and E. coli plasmid pGEM-3 digested with BgIII and BamHI respectively. The shuttle plasmid pSE-3 could replicate and express its neomycin resistance in both Streptomyces and E. coli well. The pSE-3 has opposed promoters containing bacteriophage ST6 and T7, the restriction enzyme digestion showed that the pSE-3 has a single site with HindIII and EcoRI respectively, it is very useful for the cloning and expression of the valuable gene inserts. The pSE-3 is stable in both of Streptomyces and E. coli after re-transformed pSE-3 is re-transformed from Streptomyces into E. coli and some 50 generations are propagated.

Escherichia coli↗
PubMed1990

[Cloning and expression of E. coli glucose isomerase gene in Streptomyces lividans].

E. coli glucose isomerase gene was cloned into Streptomyces lividans using shuttle plasmid vector pSE-3. First plasmid pXI203 was constructed in E. coli using plasmids pXI200 (containing 1.6 kb glucose isomerase gene) and pGEM-3 digested with EcoR1. Then, recombinant plasmid pSEX100 was also constructed in E. coli using plasmids pXI203 and pSE-3 digested with HindIII. When the pSEX100 was transformed into Streptomyces lividans protoplasts, recombinants were obtained on R5YE medium containing 50 micrograms/ml neomycin and 50 micrograms/ml thiostrepton. The results showed that the E. coli glucose isomerase gene cloned and expressed in Streptomyces lividans via the analysis of restriction enzyme digestion as well as the detection of the glucose isomerase activity.

Aldose-Ketose Isomerases↗
PubMed1987

Phenotypically heterogeneous deletion of the ABH antigen from the transformed bladder urothelium. A scanning electron microscope study.

The deletion of ABH blood group antigens from the luminal surface of the bladder mucosa in cases of well differentiated transitional cell carcinomata, and the formation of pleomorphic microvilli have both been associated with aggressive biological behaviour and invasiveness of the tumors. We have studied cold cup biopsies from 8 normal mucosae and 17 papillary transitional cell carcinomata of the urinary bladder. The aim of our study was to correlate the formation of uniform or pleomorphic microvilli with the extent of deletion of the ABH blood group antigens on the surface of normal and transformed bladder urothelium. Immunogold scanning electron microscopy (SEM) in the backscattered electron (BE) imaging mode was used for this purpose. In the normal urothelium, uniform labeling of the luminal cells was demonstrated. In well differentiated tumors, the superficial cells exhibited uniform microvilli and a heterogeneous expression of the ABH antigens, giving characteristic 'mosaic' patterns of the antigenic labeling across the mucosal surface. These patterns were sharply delimitated at cell junctions when viewed by SEM; these observations were confirmed by transmission electron microscopy. In higher grade tumors, decreased ABH antigen expression, pleomorphic microvilli and/or featureless luminal cells were observed. In the transformed urothelium, the formation of uniform microvilli appeared to precede the loss of ABH antigen in most cases.

ABO Blood-Group System↗
PubMed1986

Inheritance of immunity in mice to challenge infection with Nematospiroides dubius.

Two lines of mice (Mus musculus) were selectively reared over 10 generations for high (H) and low (L) levels of immune response to Nematospiroides dubius, an enteric nematode parasite. Filial and backcross families were derived from the two parent lines. The mode of inheritance of the trait, immune response to challenge infection with N. dubius, was analysed by comparing the levels of infection in the parental, filial and backcross (BC) families of mice. The immunity of the F1 mice was found to be dissimilar to both parents, but was closer to the H value than to the level of immunity in the L mice. The backcross to H progeny showed levels of immunity approaching that of the H mice, whereas only two of four backcross to L families were low immune responders. Analysis of these results indicated that the inheritance of immunity in these mice to challenge infection with N. dubius was quantitative, partially dominant for high immune response, and additive, in nature.

Animals↗
PubMed1986

Management of coexisting Hodgkin's disease and pregnancy.

The management of pregnant women with active Hodgkin's disease (H.D.) should be individualized depending on the stage, the presence of infradiaphragmatic involvement, and age of gestation. Seventeen women aged 16-31 years with coexisting H.D. and pregnancy were followed between 1969 and 1982. H.D. was diagnosed during pregnancy in 15 patients and two became pregnant while on treatment. Seven women whose pregnancies were allowed to proceed uninterrupted were irradiated to supradiaphragmatic sites to doses of 1,500-2,000 rad during the second or third trimester; all had full term spontaneous normal deliveries and normal infants. Fetal doses ranged from 2-50 rad. Two patients treated with Vinblastine throughout three pregnancies delivered normal full term infants. Pregnancy was interrupted in six patients at 6-20 weeks of gestation for various reasons. In spite of several months delay in initiation of definitive therapy, the outcome of H.D. was not adversely affected in the majority of uninterrupted pregnancies as evidenced by long term disease-free survivals of 6-11 years in four of seven patients who were irradiated; the children now aged 6-11 years are also alive and reported normal.

Adolescent↗