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Biomedical subjects

J H Zhou

Publications and source records attributed to J H Zhou.

At least 19 recordsLinked to original sources
PubMed1997

Epstein-Barr virus BHRF1 prohibits the cells of nasopharyngeal carcinoma from apoptosis.

Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC). The BHRF1 EBV protein is expressed at high levels in productively infected cells and certain latently infected cells. In order to investigate the effect of expression of BHRF1 on the biological behaviour of NPC cells, we constructed the BHRF1 high expression vector and transfected it into the NPC cell line, CNE2. Then, the alteration of proliferation and apoptotic rates in the cells were tested before and after camptothecin treatment. After treatment by camptothecin, BHRF1-CNE2 cells could constantly and slowly proliferate and its apoptotic rate was less than in control groups, and the number of cells in the G phase decreased and in the S phase increased. So, it suggests that BHRF1 expression can enhance the resistibility of CNE2 cells to DNA-damaging agents that cause apoptosis.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Purification and activity of recombinant chicken stem cell factor produced by using a baculovirus vector.

Stem cell factor is a pleiotropic cytokine that plays an essential role in the development of hematopoietic cells, germ cells, and melanocytes. To obtain recombinant soluble chicken stem cell factor (chSCF), a baculovirus containing the cDNA encoding chSCF polypeptide from amino acids -25 to 170 was constructed. The chSCF produced in insect cells infected with the virus was purified by ion exchange column chromatography. The ability of the purified protein to induce the outgrowth of neurites from chicken dorsal root ganglia cultured in vitro was demonstrated.

Animals↗
PubMed1996

[Effect of microinjection of angiotensin II into area postrema on renal sodium excretion].

It has been known that area postrema (AP) possesses angiotensin II (A II) receptors and senses directly the change of blood A II level. The effect of microinjection of A II into the AP on renal sodium excretion was studied in the present investigation. Our experimental results show that microinjection of A II (2, 20 ng) increases GFR, RPF and UNaV (P < 0.05). These changes can be abolished by A II antagonist, saralatin and renal denervation (P < 0.05). However microinjection of A II (20 ng) into NTS produces no such changes. These results strongly suggest that the A II induced changes of renal hemodynamics and urine sodium excretion are mediated through AP.

Angiotensin II↗
PubMed1995

Structure-activity relationships of cytotoxic cholesterol-modified DNA duplexes.

Short DNA duplexes with cholesterol linked at the 3'-terminus of each strand have unique, selective cytotoxic properties. The structural requirements for biological activity were explored through chemical synthesis of analogs and testing in cultured hepatoma cells. Effects of modifications to the sequence, backbone, 3'-sterol, 3'-linker, and 5'-terminus were evaluated. Self-complementary 3'-modified oligodeoxynucleotide (ODN) 10-mers were prepared from solid supports bearing the modification and linker of interest. Any changes to the normal phosphodiester backbone were poorly tolerated. The presence of cholesterol or a closely related sterol was an absolute requirement for activity. The length and position of attachment of the linker to cholesterol was important, with longer linkers showing reduced activity. Large, lipophilic groups at the 5'-terminus gave reduced cytotoxicity and poor solubility properties. The short length and unique structure of these ODNs allowed efficient automated synthesis on a 400 mumol scale and simplified purification.

Antineoplastic Agents↗
PubMed1995

Lysis of small cell carcinoma of the lung (SCCL) cells by cytokine-activated monocytes and natural killer cells in the presence of bispecific immunoconjugates containing a gastrin-releasing peptide (GRP) analog or a GRP antagonist.

Lung cancer remains the leading cause of cancer deaths in the United States. We have developed a new immunotherapeutic approach to the treatment of small cell carcinoma of the lung (SCCL) by targeting the gastrin-releasing peptide receptor (GRP-R) expressed on the surface of these cells. Bispecific immunoconjugates were constructed by chemical fusion of a GRP analog or a GRP antagonist with monoclonal antibodies directed to the cytotoxic trigger molecules Fc gamma RI and Fc gamma RIII on various immune effector cells. We demonstrated that these bispecific immunoconjugates bound to target SCCL cells in a dose-dependent manner. In the presence of these immunoconjugates, more than 80% of SCCL cells were lysed by cytokine-activated monocytes and natural killer (NK) cells measured by a 51Cr-release assay. These data indicate that bifunctional antibodies targeting GRP may have clinical use.

Antibodies, Bispecific↗
PubMed1995

[Pharmacokinetics of contragestazol (DL-111-IT), a new non-steroid antifertility agent in monkeys].

The pharmacokinetics of contragestazol, an early pregnancy temperating agent [3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole, DL-111-IT] was studied in Rhesus monkey. The blood concentration of DL-111-IT was determined by coupled column system HPLC method. Using an aqueous vehicle (20% cremophor EL in saline) DL-111-IT was injected intravenously to monkeys at doses of 25, 12.5 and 6.3 mg.kg-1. Blood drug concentration were measured. Using a programmable calculator the calculated pharmacokinetic parameters were as follows: alpha 1.83 h-1, 4.71 h-1 and 3.61 h-1, beta 0.15 h-1, 0.08 h-1 and 0.09 h-1; T1/2 beta 6.63 h, 10.2 h and 10.1 h; AUC 9.54 micrograms.h-1.ml-1, 3.94 micrograms.h-1.ml-1 and 3.75 micrograms.h-1.ml-1. An oil solution of DL-111-IT was injected intramuscularly in monkeys at doses of 50, 25 and 12.5 mg.kg-1. Its blood concentrations were determined at 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 and 24 h after administration. From the time vs concentration curve, the pharmacokinetic parameters obtained were as follows: Ka 0.98 h-1, 1.03 h-1 and 1.45 h-1; Ke 0.42 h-1, 0.37 h-1 and 0.60 h-1; T1/2Ke 1.66 h, 1.90 h and 1.16 h; T (peak) 1.52 h, 1.57 h and 1.09 h; AUC 4.86 micrograms.h-1.ml-1, 5.61 micrograms.h-1.ml-1 and 1.74 micrograms.h-1.ml-1.

Abortifacient Agents, Nonsteroidal↗
PubMed1995

[Metallothionein and medicine].

Metallothioneins are attractive substances. One of the features of these proteins is the inducibility in response to heavy metals, to a great variety of metabolites and to stress factors. In mammalia, their synthesis may be induced by interleukin-6 in response to inflammation. Metallothionein could prevent renal toxicity of cDDP without compromising its anticancer activity. However, metallothionein is also implicated in the resistance to cDDP. There are now good evidences that metallothionein is involved in many diseases, such as inflammatory bowel disease, toxemia of pregnancy, liver disease, etc.

Animals↗
PubMed1995

Effects of Rehmannia glutinosa polysaccharide b on T-lymphocytes in mice bearing sarcoma 180.

AIM: To study immuno-antitumor action mechanism of RGP-b. RGP-b (Rehmannia glutinosa polysaccaride b) is a new component isolated from the herb, had an average molecular mass of 160 kDa and 5 kinds of monosaccharides as acid-splitting products. Its HPLC showed a main sharp peak at 162 kDa. METHODS: The kinetic effects of RGP-b on IL-2 secretion, cytotoxic T-lymphocyte (CTL) activities and L3T4+, lyt-2+ T-lymphocyte subset in mice bearing S180 were observed. RESULTS: RGP-b 10 or 20 mg kg-1 ip obviously attenuated the decrease of CTL cytotoxity caused by excessive tumor growth on d 9 after the administration, but only partly ameliorated the descent of IL-2. Its effect on lyt-2+ subset was quite parallel with that on CTL cytotoxity. RGP-b kept the ratio of L3T4+ to lyt-2+ subset lower than that of control. CONCLUSION: Improving the production of lyt-2+ CTL and its cytotoxity were an essential immuno-antitumor mechanisms of RGP-b.

Animals↗
PubMed1995

Monocyte-mediated lysis of acute myeloid leukemia cells in the presence of the bispecific antibody 251 x 22 (anti-CD33 x anti-CD64).

Immunotherapy using bispecific antibodies (BsAb) to direct immune effector cells toward target tumor cells has been shown to be effective in a number of studies. Several immune trigger molecules have been characterized. Among them, FcgammaRI appears to play an important role in antibody-dependent cellular cytotoxicity. It is expressed mainly on monocytes, macrophages, and neutrophils under certain clinical situations. The expression of FcgammaRI can be regulated by a variety of cytokines, primarily by IFN-gamma. Recent studies have shown that granulocyte-colony-stimulating factor (G-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) can increase the number of the FcgammaRI-positive monocytes, increase the expression of FcgammaRI on circulating neutrophils after in vivo infusion, and greatly enhance the cytotoxic activity of circulating neutrophils. CD33 is a glycoprotein expressed on the cell surface of mature monocytes, myeloid progenitor cells, and myeloid leukemic blasts, but not on the earliest hematopoietic progenitor cells and other normal tissues. Herein, we report the construction of a BsAb, 251 x 22, by conjugating an anti-CD33 mAb (mAb 251) to an anti-FcgammaRI mAb (mAb 22). The BsAb 251 x 22 is capable of enhancing the cytotoxicity of several leukemia cell lines by cytokine-activated monocytes. Our data also show that G-CSF- and GM-CSF-stimulated monocytes can mediate cytotoxicity of target leukemia cells comparable to that of IFN-gamma-stimulated monocytes. The expression of FcgammaRI on monocytes after 24-h in vitro incubation with G-CSF and GM-CSF was increased, although not significantly. Prolonged incubation of monocytes with G-CSF for 48 h significantly increased the FcgammaRI expression. Because humanized anti-CD33 and anti-FcgammaRI mAb are available, and because GM-CSF and G-CSF have been used widely for patients after chemotherapy to stimulate the recovery of myeloid hematopoiesis, additional clinical development of this project is feasible. A BsAb comprised of humanized anti-CD33 and anti-FcgammaRI could have clinical application in the treatment of myeloid leukemia, especially in the management of minimal residual disease.

Acute Disease↗
PubMed1994

Discovery of short, 3'-cholesterol-modified DNA duplexes with unique antitumor cell activity.

A new class of modified oligodeoxynucleotides with unique, selective cytotoxic properties has been discovered. Self-complementary, 3'-cholesterol-modified oligodeoxynucleotides caused morphology changes and death in certain cancer cell lines, whereas other cell lines were unaffected. Susceptible cells were killed in a dose-dependent manner at submicromolar concentrations. Optimum potency was exhibited by phosphodiester duplexes approximately 10 base pairs in length, and base composition was important only in the context of duplex stability. Phosphorothioate analogues were less potent. Although the molecular mechanism of action of these unique compounds is not yet known, they offer potential applications in cancer therapy and in studies of cell death. In addition, the path toward elucidation of the structure-based biological activity of these oligonucleotides should be especially instructive for researchers studying sequence-specific effects.

Animals↗
PubMed1994

Cloning and characterization of cDNAs encoding two normal isoforms of bovine stem cell factor.

The cDNA clones encoding two isoforms of bovine stem cell factor (bSCF) were obtained using reverse transcriptase-polymerase chain reaction, and their sequences were determined. The deduced amino acid sequences of the longer and shorter isoforms of bSCF consist, respectively, of 274 and 246 residues and show a high degree of identity to those of SCFs of different animal species. Northern blot analysis with the cDNA revealed the expression of a 5.8 kilobase bSCF RNA in fetal bovine tissues.

Amino Acid Sequence↗
PubMed1994

Involvement of lipid peroxidation in necrosis of skin flaps and its suppression by ellagic acid.

To evaluate the pathogenesis of lipid peroxidation in skin-flap necrosis and to select a novel herbal antioxidant to suppress lipid peroxidation and salvage the flaps, in vitro and in vivo experiments were instituted. In vitro studies revealed (1) the potentiality of the cutaneous microsomal system (vesicular fragment of endoplasmic reticulum) to generate oxyradicals by FeCl3 (oxidative agent), since NADPH-dependent lipid peroxidation was elevated time-dependently, (2) suppression of microsomal lipid peroxidation by herbal antioxidants (dose- and time-dependently), further supporting the theory of oxyradical-induced lipid peroxidation in the skin, and (3) that ellagic acid showed the strongest response, with curcumin, chlorogenic acid, and alpha-tocopherol (tocopherol) being moderate, and ferulic acid and gallic acid remaining weakest. Thus ellagic acid, curcumin, chlorogenic acid, and tocopherol at doses of 10, 60, 80 and 100 microM (twice I50, the dose which could inhibit lipid peroxidation by 50 percent) were chosen for in vivo assessments, respectively. In vivo studies were performed using rat back skin random flaps (70 x 15 mm and based anteriorly) and circular island flaps (20 mm in diameter and raised on superficial epigastric vessels). Control flaps were painted with a Tris-ethanol solution, and test flaps were painted with either ellagic acid, curcumin, chlorogenic acid, or tocopherol (above-mentioned doses per 250 microliters of Tris-ethanol per 300 mm2 of flap surface 1 hour before the operation and once a day for 3 postoperative days). Doses, frequency, and period of drug application were based on in vitro and in vivo pilot experiments. The results were as follows: (1) a direct and time-dependent relation was noticed between lipid peroxide levels and the rate of necrosis in both types of flap; (2) time-dependent elevation of lipid peroxide levels of skin, subcutaneous fat, and exudate of island flaps during ischemia and those of skin and subdermal fat after reperfusion indicated pre- and post-reflow states of lipid peroxidation rather than the original conception of merely reperfusion state; and (3) in good agreement with the results of in vitro experiments, ellagic acid exerted the strongest effect to suppress lipid peroxide levels of skin and to augment the viability of random flaps more than that of island flaps.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

[Pre- and postoperative NK cell number and plasma levels of TNF and PGE2 in patients with esophageal carcinoma and their clinical significance].

The number of NK cell in peripheral blood, plasma levels of TNF and PGE2 were determined in 67 patients with esophageal squamous cell carcinoma of various stages (II, III, IV) before and after operation, in 22 postoperative follow-up patients and in 20 healthy volunteers. The findings showed a significantly decreased number of NK cells and higher levels of TNF and PGE2 in patients with cancer compared with the healthy control subjects (P < 0.01). The three parameters were found to be closely related to the TNM staging of the tumors. The number of circulating NK cells increased and the plasma TNF and PGE2 levels decreased in patients after radical operation after compared with the preoperative ones, but didn't reach the normal levels. Those who developed tumor recurrence or metastases had a fall in NK cell number and a rise in the plasma TNF and PGE2 levels compared with disease-free patients and normal controls. Moreover, the decrease of NK cell number and increase of TNF, PGE2 levels occurred 2-8 months (mean 5 months) before relapse or metastases was clinically diagnosed. Additionally, the NK cell number was found to be negatively correlated with the serum PGE2. We would conclude that determination of number of circulating NK cells and plasma TNF and PGE2 concentration is of great significance in assessing prognosis and monitoring early tumor recurrence or metastasis.

Carcinoma, Squamous Cell↗
PubMed1993

Sequence of a cDNA encoding chicken stem cell factor.

Stem cell factor (SCF) is a polypeptide growth factor and the ligand for the c-kit proto-oncogene product. We cloned a chicken cDNA encoding a protein homologous to the mouse and human SCFs. The deduced amino acid (aa) sequence shows 53 and 52% identity to the mouse and human SCFs, respectively.

Amino Acid Sequence↗
PubMed1993

Thymus-neuroendocrine-liver pathway.

In order to investigate the influence of the thymus on liver functions, we used adult thymectomized rats as a model and supplemented the animals with either thymic extracts or sex hormones. Male thymectomized rats exhibited a decrease in liver microsomal cytochrome P-450 and aminopyrine-N-demethylase activities. There was also a decrease in the levels of hypothalamic luteinizing hormone-releasing hormone (LHRH), plasma luteinizing hormone (LH) and testosterone. Supplementation of testosterone propionate to these animals restored their liver P-450 and demethylase activities to normal levels. Female thymectomized rats showed an increase of liver malondialdehyde (MDA), accompanied by a decrease of liver superoxide dismutase (SOD) and glutathione (GSH), and a decline of fluidity and calcium ion uptake in liver microsomal and mitochondrial membranes. There was also a decline in hypothalamic LHRH and plasma estradiol. Supplementation of thymic extract to female thymectomized rats decreased the liver MDA, increased the liver GSH, and restored the microsomal and mitochondrial membrane fluidity and calcium ion uptake. The decrease of liver MDA was also achieved by administration of estradiol benzoate. The data suggest that the thymus may influence liver functions through the hypothalamus-pituitary-gonad axis. Thus, a new 'thymus-neuroendocrine-liver pathway' is proposed that further affirms the significance of the thymus on maintaining homeostasis and integrative functions in the body.

Animals↗