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Biomedical subjects

Z Zhu

Publications and source records attributed to Z Zhu.

At least 361 records · Page 20Linked to original sources

[Effect of dietary selenium and germanium on the precancerous lesion in rat glandular stomach induced by N-methyl-N'-nitro-N-nitrosoguanidine].

N-Methyl-N'-nitrosoguanidine (MNNG) was administered (100 mg/L) in drinking water in 100 Wistar rats for 24 weeks to induce the precancerous lesion in glandular stomach. 77 rats with the precancerous lesion in glandular stomach were divided into 3 groups randomly at the 25 thweek. Yeast selenium (Yse, 4 mg/L) and carboxyethyl germanium sesquioxide (Ge-132, 600 mg/L) in drinking water were administered respectively in the corresponding treatment groups: 100 ml/MNNG in drinking water was administered in the treatment group, and 100 ml/MNN in drinking water was administered in the treatment group and control group for another 5 weeks. The experiment ended at the end of the 37th week. The results showed that the incidence of glandular stomach cancer in the Yse group was significantly lower than that in the control group; the infiltrating depth of glandular stomach cancer in the Yse group and the Ge-132 group was remarkably shallower than that in the control group. These findings suggest that Yse and Ge-132 have some preventive effect on the precancerous lesion in rat glandular stomach induced by MNNG.

Animals↗

Study on insulin resistance in TCM treatment of noninsulin-dependent diabetes mellitus.

In the present paper, it is advanced that in TCM treatment of noninsulin-dependent diabetes mellitus (NIDDM), insulin resistance must be studied; and it is held that reversing or relieving of insulin resistance is the ultimate aim for treating NIDDM, and looking for the prescriptions of reversing the insulin resistance is an urgent task. Therefore, establishing the indexes of comprehensive assessment for the insulin resistance and the related models of the disease is the basis and prerequisite for the study.

Animals↗

[Effects of adenosine on cochlear function in guinea pigs].

As a neuromodulator, adenosine is able to decrease the release of most neurotransmitters and plays a role of negative feedback regulation. In the present experiment, the effects of adenosine, and its uptake inhibitor dipyridamole and antagonist theophylline on cochlear potentials were investigated by means of perilymphatic perfusion. 0.01 mmol/L adenosine and dipyridamole was shown to suppress compound action potentials (CAP) and cochlear microphonics (CM). The amplitudes of CAP and CM were decreased under high sound intensity stimulation. The I/O function curve was shifted toward the right and the N1 peak latency of CAP was prolonged. 1 mmol/L theophylline showed opposite effects. All these changes are reversible after washing out of the artificial perilymphy. Normal endocochlear potentials (EP) and anoxia induced negative EP (N-EP) were not changed significantly, while the rapid response of EP to noise exposure, i.e. a rapid fall with onset of noise (EP-on) and a rapid increase with offset (EP-off), could be suppressed by adenosine. These results suggest that adenosine is an inhibitory neuromodulator subserving a negative feedback role in the regulation of cochlear function.

Adenosine↗

[Detection of p53 gene mutation in bronchial biopsy samples from lung cancer patients with polymerase chain reaction-single strand conformation polymorphism-silver staining method].

In order to diagnose lung cancer at gene level, bronchial biopsy specimens from lung cancer patients, who were diagnosed by pathologic method using biopsy specimens from the same site, were used for detection of p53 gene mutation by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP)-silver staining method. 15 of 25 (60%) specimens were found to be positive. In 10 small cell lung cancer specimens, 7 were positive; in 15 non-small lung cancer specimens, 8 were positive. These results coincided with those of other reports using surgical specimens and sequencing method. Clinical analysis showed no correlation between SSCP positivity and the patients' clinical data such as age, sex, smoking habit, stage of tumor at the time of diagnosis. It is concluded that a small piece of bronchial biopsy specimen could be used to detect p53 gene mutation instead of surgical specimens and this method might be used as an adjunct to cancer screening or for a gene diagnosis prior to gene therapy. In comparison with the routine radionuclide labelled method, silver staining method has the advantage of being simple, quick, economic, safe and convenient for clinical use.

Biopsy↗

[A clinicopathological observation of 15 cases of tuberculosis of the appendix].

OBJECTIVE: To study the clinicopathological features and diagnosis of tuberculosis of the appendix. METHOD: Fifteen cases (0.27%) with tuberculosis of appendix selected from 5,621 histopathologically examined appendectomy specimens between June 1959 and May 1995 were analyzed retrospectively. RESULTS: All the cases with tuberculosis of appendix were commonly occurred in the young (< or = 34 years in 12 cases) and in females (in 11 cases). They were usually secondary to tuberculosis elsewhere in the abdomen. By microscopy, proliferative type of the lesions were found in 11 cases, while ulcerative type in 4 cases. Fourteen cases (accounting for 93%) were clinically misdiagnosed. It was difficult to be differentiated from chronic appendicitis, tuberculosis or tumor of the ileocecum and malignant tumor of the appendix. CONCLUSIONS: Definite diagnosis of tuberculosis of the appendix mainly depend on the histopathological examination. It is recommended that in order to avoid misdiagnosis, all the surgically removed appendix specimens should be histopathologically examined, no matter whether the specimens are macroscopically normal or not.

Adolescent↗

Modification of an ion-paired high pressure liquid chromatography for ticarcillin in human serum.

AIM: To develop a new HPLC assay for the clinical pharmacokinetic study of ticarcillin in human. METHODS: Reverse phase ion-paired HPLC was developed with a Novapak C18 column. The mobile phase consisted of 20% of acetonitrile and 80% of phosphate buffer 10 mmol.L-1 (pH 2.0-2.5) containing tetrapentylammonium bromide of 1 mmol.L-1. The analysis was monitored at 225 nm and the flow rate of the mobile phase was 0.8 mL.min-1. Cefoxitin was used as an internal standard. The sample volume was 200 microL of serum. RESULTS: The assay was linear in the range of 2-80 mg.L-1. The intrarun coefficients of variation (CV) for a ticarcillin 5 mg.L-1 check sample was 4.2% (n = 10), and 2.7% for a 60 mg.L-1 check sample (n = 10), respectively. The inter-run CV (n = 6) were 1.6% (5 mg.L-1) and 2.3% (60 mg.L-1), respectively. The average recovery of the assay was 96.6%. CONCLUSION: This assay was sensitive, precise, and accurate for evaluating the clinical pharmacokinetics of ticarcillin.

Chromatography, High Pressure Liquid↗

POU-domain sequences from the flatworm Dugesia tigrina.

Redundant primers matching well-conserved sequences within vertebrate and invertebrate POU genes were used in the PRC (polymerase chain reaction) to detect three different POU-domain-containing genes within the genome of the flatworm, Dugesia tigrina. Two of these genes appear to be close homologues of class-III POU genes previously identified in Dugesia japonica, while the third represents a new class-III POU gene. Nucleotide sequences encoding highly related POU domains within the two species of planaria exhibited a surprisingly poor degree of shared identity. Since only class-III POU genes have been observed to date in flatworms, these genes may represent ancestral versions of the multiple classes of POU genes that exist in vertebrates, and may play important roles in the development of metazoan nervous tissue.

Amino Acid Sequence↗

Identification of heavy chain residues in a humanized anti-CD3 antibody important for efficient antigen binding and T cell activation.

A previously identified humanized anti-CD3 Ab variant, v9, binds T cells with > 100-fold higher efficiency than the original variant, v1, and almost as efficiently as a chimeric molecule containing corresponding murine variable domains. Variants v1 and v9 differ at six positions in the H chain second CDR. Here a mutational analysis was used to identify which of these six replacements are primarily responsible for the difference in binding efficiency. These anti-CD3 variants were used to probe the relationship between Ag binding efficiency and potency in stimulating T cell proliferation. The human to mouse mutations T57S and V63F increase the binding efficiency of variant v1 for T cells by 8- and 12-fold, respectively, and together in variant M18 enhance binding by 26-fold to within 4-fold of variant v9. A framework mutation, 169L, was identified that enhances the binding of variants v1 and M18 by 14- and 3-fold, respectively. The Ag binding efficiencies of anti-CD3 variants correlate directly with their potencies in stimulating the proliferative activity of both resting human PBMC and IL-2-activated human T lymphocytes. Humanized variant v9 is equipotent to the murine parent Ab in stimulating ATL activity. PBMC activated by variants v1 and v9 IgG in a short term culture are equally cytotoxic against human breast carcinoma cells. Thus, high efficiency Ag binding by anti-CD3 variants is important for stimulating efficient T cell proliferation, but not cytotoxicity, in vitro.

Amino Acid Sequence↗

Engineering high affinity humanized anti-p185HER2/anti-CD3 bispecific F(ab')2 for efficient lysis of p185HER2 overexpressing tumor cells.

We previously constructed a humanized anti-p185HER2/anti-CD3 bispecific antibody variant, BsF(ab')2 v1 which retargets the cytotoxic activity of human T cells in vitro against human breast tumor cells which overexpress the p185HER2 product of the HER2/neu (c-erbB-2) protooncogene. Subsequently we identified an improved anti-CD3 variant, v9, which binds to T cells with approx. 100-fold higher affinity than the original variant, v1. Here we demonstrate that BsF(ab')2 v9 is more potent than BsF(ab')2 v1 in stimulating the proliferation of both resting peripheral blood lymphocytes (PBL) and IL-2-activated, long-term cultured T lymphocytes (ATL). In addition, at low concentrations (0.01-1 ng/ml) BsF(ab')2 v9 is much more efficient than BsF(ab')2 v1 in directing lysis of p185HER2-overexpressing tumor cells by IL-2 activated PBL. In contrast, at higher concentration BsF(ab')2 v9 and BsF(ab')2 v1 have similar potency in retargeted cytotoxicity. At BsF(ab')2 v9 concentrations of > or = 1 ng/ml the susceptibility of p185HER2-expressing tumor cells to lysis is apparently independent of the level of p185HER2 expression. At lower concentrations of BsF(ab')2 v9 and/or lower ratios of effector to target cells the extent of lysis is reduced, in some cases improving the selectivity of lysis of high p185HER2 expressors over low expressors. Thus selection of a high affinity anti-CD3 arm is likely important in the design of BsF(ab')2 for retargeting the cytotoxicity of T cells to tumors. The dose of BsF(ab')2 v9 in any future clinical evaluation will require optimization to maximize anti-tumor efficacy whilst minimizing potential toxicity against normal tissue expressing p185HER2.

Antibodies, Bispecific↗

MacMARCKS mutation blocks macrophage phagocytosis of zymosan.

A major protein kinase C substrate, MacMARCKS (F52, MPR), was examined for its role in phagocytosis. In macrophage-phagocytosing zymosan particles, MacMARCKS was concentrated around nascent phagosomes as detected by immunofluorescent microscopy. The effector domain of MacMARCKS contains the phosphorylation sites, a calmodulin binding site, as well as a putative actin binding site. Stable J774 macrophage cell lines constitutively expressing effector domain deletion mutants of MacMARCKS were generated. When given zymosan particles, these transfectants showed approximately a 90% reduction in their phagocytic capacity. The receptor-mediated endocytosis of acetylated low density lipoproteins, however, was not affected by the mutant. These results strongly suggest the involvement of MacMARCKS in macrophage phagocytosis.

Cell Adhesion Molecules↗

Infection of cells by varicella zoster virus: inhibition of viral entry by mannose 6-phosphate and heparin.

Envelope glycoproteins of varicella zoster virus (VZV) contain mannose 6-phosphate (Man6P) residues. We now report that Man6P competitively and selectively inhibits infection of cells in vitro by cell-free VZV; furthermore, dephosphorylation of VZV by exposure to alkaline phosphatase rapidly destroys infectivity. Cells are also protected from VZV in a concentration-dependent manner by heparin (ED50 = 0.23 micrograms/ml; 95% confidence limits = 0.16-0.26 microgram/ml) but not by chondroitin sulfate. Both heparin and Man6P are protective only when present about the time of inoculation. Heparin but not Man6P interferes with the attachment of VZV to cell surfaces; moreover, VZV binds to heparin-affinity columns. These data are compatible with a working hypothesis, whereby VZV attaches to cell surfaces by binding to a heparin sulfate proteoglycan. This binding stabilizes VZV, making possible a low-affinity interaction with another Man6P-dependent receptor, which is necessary for viral entry.

Alkaline Phosphatase↗

Effect of extracellular Mg2+ concentration on agonist-induced cytosolic free Ca2+ transients.

The modulating effects of extracellular Mg2+ concentration ([Mg2+]o) on vascular contraction are well known. In the present study it was tested how the changes in cytosolic free Ca2+ concentration ([Ca2+]i) induced by various agonists are modified by changes in [Mg2+]o. Extracellular Mg2+ deprivation increased the [Ca2+]i response to arginine vasopressin, to angiotensin II and to thapsigargin, but not to 5-hydroxytryptamine and noradrenaline. Withdrawal of extracellular Ca2+ revealed that extracellular Mg2+ deprivation increased Ca2+ influx, but not Ca2+ release from cellular stores. The findings demonstrate that different responses of [Ca2+]i to agonists may underlie the modulating effect of [Mg2+]o on vascular contraction.

Angiotensin II↗

U.S. farm women's participation in breast cancer screening practices.

BACKGROUND: Surveys of women in the general population indicate that women are being screened for breast cancer at a much lower rate than recommended. There has been a concern that women living in rural areas may be screened for breast cancer even less often than women in urban or suburban areas because of reduced access to health practitioners. METHODS: A random sample of farm women age 40 years or older from 4 rural counties in Michigan was surveyed on knowledge, attitudes, and use of breast cancer screening. RESULTS: Six hundred eighty farm women completed a questionnaire. This was a response rate of 63.8%. The percentages of farm women who reported ever having had a mammogram, having had a mammogram in the past 3 years, and having had a mammogram in the last year were 80.6, 73.7, and 51.9%, respectively. The frequency of clinical breast examinations parallelled mammography usage at slightly higher percentages. Mammogram usage increased with higher education, income, and insurance coverage. Usage decreased in women age 75 years or older (ever 63.1%, in the last 3 years 58.2%, and in the last year 40.4%). Farm women were generally knowledgeable about symptoms and signs of breast cancer and understood the benefit of screening. There was, however, a range of answers on when to start or stop having a mammogram. Among farm women who reported not having a mammogram recently, the most important reasons were: haven't had any problems (29.4%), wasn't recommended by a doctor (14.3%), and procrastinated (11.3%). CONCLUSIONS: Farm women in this survey reported having had breast cancer screening at rates similar to or above those in the general population. Because of a limited response rate (63.5%) and the relative affluence of the farming community in the 4 counties surveyed, these results are probably not generalizable to all populations of farm or rural women.

Adult↗

Pneumoconiosis and associated medical conditions.

Hospital discharge data from Michigan for the years 1990 and 1991 were used to examine potential associations between pneumoconiosis and pulmonary hypertension, lung cancer, obstructive lung disease, and connective tissue disease among both men and women. Lung cancer, pulmonary hypertension, and obstructive lung disease were associated with coal workers' pneumoconiosis. Pulmonary hypertension and obstructive lung disease were associated with asbestosis and silicosis. Rheumatoid arthritis was associated with silicosis. The potential is suggested that misdiagnosis is the cause of the association between lung cancer and coal workers' pneumoconiosis.

Adult↗

Inhibition of Epstein-Barr-virus-transformed human chronic lymphocytic leukaemic B cells with monoclonal-antibody-adriamycin (doxorubicin) conjugates.

The anthracyclin antineoplastic agent doxorubicin (Adriamycin) was linked by four different methods of linkage to DalB02, an IgG1 kappa murine monoclonal antibody (mAb) against surface-associated antigens on human chronic lymphocytic leukaemia (CLL) B cells. All the four conjugates fully retained the immunoreactivity of the parent DalB02. When the inhibitory effect of these conjugates was evaluated in vitro against the target D10-1 cells (a clone derived from an Epstein-Barr-virus-transformed human CLL B cell line that binds DalB02) it was observed that one conjugate was more potent than the free drug but the others were not. When 131I-labelled unmodified DalB02 and the 131I-labelled DalB02-containing conjugate that was found to be potent were injected i.v. into nude mice bearing a subcutaneous D10-1 xenograft, the percentages of the injected dose (%ID) of both 131I-DalB02 and the 131I-DalB02-containing conjugate that localized in the tumour were much higher than the %ID of the respective preparations that localized in normal tissues of D10-1-xenografted mice. The systemic toxicity of the conjugate was less than that of the free drug. At an equitoxic dose level, this conjugate was a more effective inhibitor of established D10-1 xenografts than the free drug.

Animals↗

Effect of selenium on malignant tumor cells of brain.

Some reports have demonstrated that selenium can inhibit tumorigenesis in some tissues of animal. However, little is known about the inhibitory effect on malignant tumor cells of brain. The purpose of our study was to determine the biological effect of selenium on growth of rat glioma and human glioblastoma cell lines. Cell lines C6 and A172 were obtained from Japanese Cancer Research Resources Bank, Tokyo, Japan (JCRB). Cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% fetal calf serum at 37 degrees C in a humidified atmosphere of air and 5% CO2. Antiproliferative effects of selenium were evaluated using growth rate assay quantifying cell number by MTT assay. An antiproliferative effect of selenium was found in two cell lines, which was more effective on human A172 glioblastoma and less effective on rat C6 glioma.

Animals↗

Uptake and distribution of sodium selenite in rat brain tumor.

Eighteen weanling male Wistar rats with brain gliomas were divided into three groups, which received 0., 2.0, 5.0 ppm selenium (Se) in their drinking water. The accumulation and retention of selenium in the brain bearing tumor was investigated. Significantly higher concentrations of Se were observed in tumor tissue than normal brain tissue after exposure to sodium selenite. Tumors were observed in the 2.0 micrograms/g selenium group. The difference in selenium concentration between the tumor tissue and contralateral normal brain tissue was not influenced by the weight of brain or body, and water consumption. We observed that selenium accumulated in tumor tissue more than in normal brain tissue.

Administration, Oral↗