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Biomedical subjects

S Han

Publications and source records attributed to S Han.

At least 199 records · Page 11Linked to original sources
PubMed1998

Characterization of Y122F R2 of Escherichia coli ribonucleotide reductase by time-resolved physical biochemical methods and X-ray crystallography.

Ribonucleotide reductase (RNR) from Escherichia coli catalyzes the conversion of ribonucleotides to deoxyribonucleotides. It is composed of two homodimeric subunits, R1 and R2. R2 contains the diferric-tyrosyl radical cofactor essential for the nucleotide reduction process. The in vitro mechanism of assembly of this cluster starting with apo R2 or with a diferrous form of R2 has been examined by time-resolved physical biochemical methods. An intermediate, Fe3+/Fe4+ cluster (intermediate X), has been identified that is thought to be directly involved in the oxidation of Y122 to the tyrosyl radical (*Y122). An R2 mutant in which phenylalanine has replaced Y122 has been used to accumulate intermediate X at sufficient levels that it can be studied using a variety of spectroscopic methods. The details of the reconstitution of the apo and diferrous forms of Y122F R2 have been examined by stopped-flow UV/vis spectroscopy and by rapid freeze quench electron paramagnetic resonance, and Mössbauer spectroscopies. In addition the structure of this mutant, crystallized at pH 7.6 in the absence of mercury, at 2.46 A resolution has been determined. These studies suggest that Y122F R2 is an appropriate model for the examination of intermediate X in the assembly process. Studies with two mutants, Y356F and double mutant Y356F and Y122F R2, are interpreted in terms of the possible role of Y356 in the putative electron transfer reaction between the R1 and R2 subunits of this RNR.

Amino Acid Substitution↗
PubMed1998

On the correlation between the water diffusion coefficient and oxygen tension in RIF-1 tumors.

Water diffusion-coefficient mapping was used in conjunction with 19F inversion-recovery echo-planar imaging (IR-EPI) of a sequestered perfluorocarbon (PFC) emulsion to investigate the spatial correlation between the diffusion coefficient of water and the tissue oxygen tension (pO2) in radiation-induced fibrosarcoma (RIF-1) tumors (n = 11). The diffusion-time-dependent apparent diffusion coefficient, D(t), was determined by acquiring diffusion coefficient maps at 20 different diffusion times. Maps at four representative time points in different regions of the D(t) curve were selected for final analysis. An intravenously administered PFC emulsion, perfluoro-15-crown-5-ether, was used to generate the PO2 maps. D(t) and PO2 data were acquired with the animal breathing either air or carbogen (95% O2 - 5% CO2) to investigate the effects of increased tumor pO2 on D(t). The average increase in tumor pO2 was 22 torr when the breathing gas was changed from air to carbogen. Correlation plots generated from pixel data for D(t) (air breathing) vs D(t) (carbogen breathing) show little deviation from a slope of unity. Correlation plots of D(t) vs PO2 indicate that no correlation is present between these two parameters. This study also confirmed that necrotic tissue was best differentiated from viable tumor tissue based on D(t) maps at long diffusion times.

Animals↗
PubMed1998

Role of neuropeptide Y in cold stress-induced hypertension.

Chronic cold stress (4 degrees C) produced a sustained increase in mean arterial pressure in both normotensive and borderline hypertensive rats (BHR). The high blood pressure in BHRs was significantly reversed by a neuropeptide Y (NPY) Y1 receptor antagonist suggesting that NPY is involved in mediating stress-induced hypertension. Corresponding increases in adrenal NPY messenger RNA and NPY immunoreactivity were found during the stress; furthermore, chronic cold stress also potentiated the pressor response of rats to a subsequent acute stress test in which NPY has been shown to play a role. These results suggest that chronic cold stress-induced hypertension is mediated by elevated NPY release and vascular tone as a result of increased NPY gene expression and storage.

Adrenal Glands↗
PubMed1998

Expression of Th1/Th2 cytokine mRNA in peritoneal exudative polymorphonuclear neutrophils and their effects on mononuclear cell Th1/Th2 cytokine production in MRL-lpr/lpr mice.

Peritoneal exudative polymorphonuclear neutrophils (PEC-PMN) and mononuclear cells (PEC-MNC) were obtained from normal BALB/c and from autoimmune MRL-lpr/lpr mice (lpr) with different disease severities. The spontaneous and mitogen-stimulated expression of T-helper lymphocyte type-1 (Th1) [represented by interferon-gamma (IFN-gamma) and interleukin (IL-2)] and T-helper lymphocyte type-2 (Th2) (represented by IL-4 and IL-10) cytokine mRNA in these cells was detected by reverse transcription-polymerase chain reaction (RT-PCR). The production of these cytokines was measured by enzyme-linked immunosorbent assay (ELISA). We found that the spontaneous expression of Th1/Th2 cytokine mRNA in PEC-PMN from autoimmune mice was progressively increased in parallel with disease severity but was not changed by lipopolysaccharide (LPS) stimulation. By contrast, spontaneous expression of Th1/Th2 cytokine mRNA in PEC-MNC from these mice was progressively decreased in parallel with disease severity but retained the responsiveness to phytohaemagglutinin (PHA) stimulation. To determine the effect of PEC-PMN on Th1/Th2 cytokine production by PEC-MNC, autologous PEC-PMN and PEC-MNC were co-cultured at MNC:PMN ratios of 5:0, 4:1, 3:2, 2:3, 1:4 and 0:5 with PHA stimulation for 24 hr. The production of cytokines at each ratio was compared with the expected value, by calculation. We found that PEC-PMN from autoimmune mice progressively suppressed the production of IL-4, IL-10 and IFN-gamma whereas the production of IL-2 was enhanced by autologous MNC in parallel with disease severity. These results suggest that a reciprocal relationship exists in the expression of Th1/Th2 cytokine mRNA between PEC-PMN and PEC-MNC in lpr mice in parallel with disease severity. Autoimmune PEC-PMN can exert significant modulatory effects on Th1/Th2 cytokine production by autologous MNC in stimulation.

Animals↗
PubMed1998

Traditional and evidence-based acupuncture: history, mechanisms, and present status.

BACKGROUND: In 1983, the Southern Medical Journal advised its readers that a scientific basis might underlie the popular practice of ancient Chinese acupuncture. Recent studies have proven this to be correct, and a 1997 National Institutes of Health consensus panel recommended acupuncture as a useful clinical procedure. METHODS: Pertinent articles in the literature were reviewed, including our own research. Significantly, we had access to recent important studies from China. RESULTS AND CONCLUSIONS: Most of the 10,000 acupuncturists in the country today practice metaphysically explained "meridian theory" acupuncture using needles to supposedly remove blockages of a hypothesized substance "Qi." Scientific research has shown that healing is not by manipulating Qi but rather by neuroelectric stimulation for the gene expression of neuropeptides. Needles are not necessary. Evidence-based neuroelectric acupuncture requires no metaphysical rituals. It is a simple, useful clinical tool for pain modulation and other conditions and can be easily taught to physicians.

Acupuncture Therapy↗
PubMed1998

Immunoglobulin gene hypermutation in germinal centers is independent of the RAG-1 V(D)J recombinase.

Antigen-driven somatic hypermutation in immunoglobulin genes coupled with stringent selection leads to affinity maturation in the B-lymphocyte populations present in germinal centers. To date, no gene(s) has been identified that drives the hypermutation process. The site-specific recombination of antigen-receptor gene segments in T and B lymphocytes is dependent on the expression of two recombination activating genes, RAG-1 and RAG-2. The RAG-1 and RAG-2 proteins are essential for the cleavage of DNA at highly conserved recombination signals to make double-strand breaks and their expression is sufficient to confer V(D)J recombination activity to non-lymphoid cells. Until very recently, expression of the V(D)J recombinase in adults was believed to be restricted to sites of primary lymphogenesis. However, several laboratories have now demonstrated expression of RAG-1 and RAG-2 and active V-to-(D)J recombination in germinal center B cells. This observation of active recombinase in germinal centers raises the issue of RAG-mediated nuclease activity as a component of V(D)J hypermutation. Here, we show that a transgenic kappa-light chain gene in a RAG-1-/- genetic background can acquire high frequencies of mutations. Thus, the RAG-1 protein is not essential for the machinery of immunoglobulin hypermutation. The genetic approaches to identifying the genes necessary for somatic hypermutation will require further studies on DNA-repair and immunodeficient models.

Animals↗
PubMed1998

Direct evidence for the role of neuropeptide Y in sympathetic nerve stimulation-induced vasoconstriction.

Neuropeptide Y (NPY) is a vasoconstrictor peptide and a cotransmitter with norepinephrine (NE) in sympathetic nerve terminals and is thought to be involved in sympathetic nerve stimulation (SNS)-induced vasoconstriction. Using BIBP-3226, a Y1 receptor selective antagonist, we examined this hypothesis in the isolated and perfused mesenteric vascular bed. SNS produced a frequency-dependent increase in perfusion pressure and concomitant overflow of NPY immunoreactivity in the perfusate. [Leu31,Pro34]NPY potentiated NE-induced and ATP-induced vasoconstriction, indicating the presence and biological action of Y1 receptors in this vascular bed. The potentiation effect of [Leu31,Pro34]NPY of the increase in perfusion pressure by NE, ATP, or SNS was prevented by BIBP-3226. In addition, SNS-induced vasoconstriction at both high and low frequencies was significantly attenuated by BIBP-3226 at a concentration that completely blocked the [Leu31,Pro34]NPY-induced potentiation of the NE- or ATP-induced vasoconstrictor effect. These results suggest that approximately 30% of vasoconstriction produced by SNS depends on NPY in the mesenteric vascular bed.

Animals↗
PubMed1998

A new method to improve in-bore middle cerebral artery occlusion in rats: demonstration with diffusion- and perfusion-weighted imaging.

BACKGROUND AND PURPOSE: In-bore middle cerebral artery occlusion (MCAO) enables investigators to acquire preischemic MRI data and to image ischemic changes immediately after occlusion. We have developed a highly successful in-bore MCAO method. This study describes the methods and pertinent techniques. METHODS: Sixty-seven Sprague-Dawley rats were subjected to temporary (n=36) or permanent (n=31) MCAO. The occluding device consisted of a supporting tubing, a driving line, and a silicone-coated 4-0 nylon suture occluder. Outside the magnet, the occluder was positioned in the carotid canal. MCAO was achieved in the magnet bore by remotely advancing the driving line until resistance was felt. Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) were acquired before and immediately after occlusion and were used to document the presence of MCAO. RESULTS: Fifty-nine (88.1%) rats were successfully occluded, demonstrating hyperintensity on DWI, perfusion deficits on PWI, and no subarachnoid hemorrhage at postmortem examination. The average values of the apparent diffusion coefficient in both the frontoparietal cortex and the lateral caudoputamen significantly decreased as early as 3 minutes after the onset of ischemia. The failures included preocclusion damage (1/67), sliding out of the occluder during occlusion (1/67), no occlusion (2/67), and arterial perforation (4/67). CONCLUSIONS: Our in-bore MCAO method is easily performed and is as successful as MCAO induced outside the magnet.

Animals↗
PubMed1998

[Development of the certified reference material of iodine in lyophilized human urine].

Urine samples from normal level and low level iodine districts were filtered, homogenized, dispensed, lyophilized and radio-sterilized. Homogeneity test, stability inspection and certification were conducted using a spectrophotometric method. The physical and chemical stability of the CRM (Certified reference material) were assessed for one year. The certified values are based on analysis made by five independent laboratories using three different principle methods. The certified values +/- uncertainties are as follows: low level is (121 +/- 14) micrograms/L, normal level is (201 +/- 11) micrograms/L.

Freeze Drying↗
PubMed1998

[The effect of ectopic HCG on microvessel density in gastric carcinoma].

OBJECTIVES: To study the effect of ectopic HCG on microvessel density in gastric carcinoma using immunohistochemical staining with anti-beta-HCG polyclonal antibody and anti-factor VIII related antigen(FVIII RAg)antibody. METHODS: A total of 40 specimens resected from patients with gastric carcinoma was investigated by immunohistochemical staining with a anti-beta-HCG polyclonal antibody and a monoclonal antibody against FVIII RAg. The expression of beta-HCG and the microvessel density(the average number of microvessel in three areas of highest vascular density at 400 x magnification) in various regions of the histologic specimens were studied. RESULTS: Fifteen (37.5%) of the 40 gastric carcinomas was positive for beta-HCG protein in tumor tissue. beta-HCG protein was negative in the tumor-adjacent and in normal tissue. The mean microvessel density was 27.4 +/- 7.1 in the tumor, 11.9 +/- 5.4 in tumor-adjacent and 4.8 +/- 1.5 in normal tissues (P < 0.05-0.01). There was a close correlation with beta-HCG positivity and microvessel density (MVD). There was no correlation between the degree of tumor cell differentiation and beta-HCG expression, nor was a correlation between it and MVD. High expression level of beta-HCG and MVD was significantly associated with hematogenous metastases. CONCLUSION: Ectopic HCG expression may have angiogenic effect which, in turn, may facilitate hematogenous dissemination of gastric cancer.

Adenocarcinoma↗
PubMed1998

Preliminary observation on the correlation between nm23 expression and Ki-67 antigen with early metastasis of human osteosarcoma.

OBJECTIVES: To detect the nm23 expression in osteosarcoma, analyze the correlation between nm23 expression and early metastasis and to study the relation between nm23 expression with tumor differentiation and cell proliferation, as defined by Ki-67 labeling. METHODS: nm23 oncoprotein expression was measured by immunohistochemical staining using formalin fixed, paraffin embedded sections of 39 surgically resected osteosarcomas and was compared with Ki-67 expression, histological findings and early metastasis. In each sample, the grading of immunoreactivity was recorded as 0, 1+, 2+ according to the percentage of nm23 and Ki-67 labeling cells respectively. RESULTS: The cases with more than 25% positive immunoreactivity of nm23 protein were detected in 48.7% of the total cases. There was no statistical difference between nm23 expression and early metastasis, but the cases with nm23 expression appeared to have a trend to get early metastasis. nm23 expression was significantly correlated with Ki-67 expression, which was associated with differentiation of the tumor cells. CONCLUSION: The role of nm23 as a tumor metastasis suppressor in osteosarcoma is less prominent. Both nm23 and Ki-67 may help predict the possibility of early metastasis in human osteosarcomas.

Adolescent↗
PubMed1998

The effect of blockage of macrophage on tumor-suppressive activity of polyactin B.

OBJECTIVE: To investigate the tumor-suppressive activity of polyactin B (PB) and the life-span of tumor bearing mice treated with PB and the anti-tumor mechanisms of PB by blockage of macrophage in vivo. METHODS: Thirty-two S180 sarcoma-bearing (s.c.) BALB/c inbred mice were divided into 4 groups, i.e., control group (8 mice), PB group (8), Trypan blue (TrB) group (8) and PB + TrB group (8). Five days after PB injection (i.p.), the tumor size of the mice was measured, and the ratio of TNA to TTA in HE section of the tumor maximal area was calculated and the pathological features of the tumors were observed. Forty S180 sarcoma-bearing (i.p.) ICR mice, which were randomly divided into 4 groups as above, were used for observation of the life-span. RESULTS: PB could strongly inhibit the growth of S180 sarcoma with the tumors regressing completely in 3 of 8 mice, prolong the life-span of mice bearing S180 sarcoma, increase the infiltration of macrophages and lymphocytes in the periphery and inside of the tumors. In addition, there were more prominent hemorrhagic necrosis, neutrophil infiltration and microthrombi in small vessels around the necrotic areas in the tumors of PB treated group. The tumor-suppressive effect of PB disappeared after macrophage system blockage with TrB. In PB + TrB, TrB, control and PB groups, the size of tumors reduced, and the life-span of mice increased in successive order. CONCLUSIONS: (1) PB is a strong activator of macrophage. (2) In vivo the tumor-suppressive effect of PB is initially mediated by PB activated macrophage system. Then other immunocompetent cells, e.g., T-cells, NK-cells, etc, activated directly and/or indirectly by PB, may play a very important role in tumor suppression. (3) PB-activated macrophages are more sensitive to TrB blockage. Therefore, using TrB + PB to block macrophage system is more effective than TrB alone. (4) Blockage of macrophage function might influence the life-span of the mice.

Animals↗
PubMed1998

[Cloning and sequencing of the Chinese bovine prion protein (PrPC) gene].

The total DNA was isolated from lymphocyte of peripheral blood of Chinese cattle. The PrPC gene was amplified by polymerase chain reaction, using two primers. It was then cloned into pGEM-T Easy Vector. The result of DNA sequencing was indicated that the 795 bp amplified fragment contains the entire PrPC coding sequence, which has no intron and is same as the published gene sequence.

Amino Acid Sequence↗
PubMed1997

V(D)J recombinase activity in a subset of germinal center B lymphocytes.

Reexpression of the V(D)J recombinase-activating genes RAG1 and RAG2 in germinal center B cells creates the potential for immunoglobulin gene rearrangement and the generation of new antigen receptor specificities. Intermediate products of V(D)J recombination are abundant in a subset of germinal center B cells, demonstrating that the kappa immunoglobulin light-chain locus becomes a substrate for renewed V(D)J recombinase activity. This recombinationally active cell compartment contains many heavy-chain VDJ rearrangements that encode low-affinity or nonfunctional antibody. In germinal centers, secondary V(D)J recombination may be induced by diminished binding to antigen ligands, thereby limiting abrupt changes in receptor specificity to B cells that are usually eliminated from the germinal center reaction. This restriction preserves efficient antigen-driven selection in germinal centers while allowing for saltations in the somatic evolution of B cells.

Animals↗
PubMed1997

HPV-16 oncogenes E6 and E7 are mutagenic in normal human oral keratinocytes.

The mutation frequency of pS189 shuttle vector plasmids is higher in human oral keratinocytes (NHOK) immortalized with cloned human papillomavirus-16 (HPV-16) genome than in primary normal NHOK (NHOK). To determine whether oncoproteins E6 and E7 of HPV-16 are responsible for the higher mutation frequency of the plasmids, we measured the mutation frequency in NHOK and in NHOK expressing the HPV-16 oncogenes (E6, E7, or E6 plus E7). We also measured the mutation frequency in NHOK expressing the E6 or E7 proteins of the non-oncogenic HPV-6b. The mutation frequency, either background or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced, in NHOK expressing the HPV-16 oncoproteins (E6, E7, or E6 plus E7) was significantly higher than in NHOK. The HPV-16 oncogenes did not alter the nature of the MNNG-induced mutations (G:C-->A:T), but increased the frequency of deletions and insertions with or without MNNG. The background or MNNG-induced mutation frequency in NHOK expressing the HPV-6b E6 or E7 proteins was the same as in NHOK. NHOK and NHOK expressing HPV6b-E6 or E7 were able to arrest the cell cycle and enhance cellular p53, p21(WAF1/CIP1), and Gadd45 levels when exposed to MNNG, whereas NHOK expressing the HPV-16 E6 oncogene did not demonstrate. NHOK expressing HPV-16 E7 were able to enhance cellular p53, p21(WAF1/CIP1), and Gadd45 levels, but failed to arrest cell cycle progression when exposed to MNNG. These data indicate that HPV-16 E6 and E7 oncogenes are mutagenic in human oral keratinocytes and enhance the mutagenic effect of MNNG. However, the E6 and E7 proteins of the 'low risk' HPV-6b did not demonstrate such an ability.

Cell Cycle↗
PubMed1997

Abnormal expression of four novel molecular markers represents a highly aggressive phenotype in breast cancer. Immunohistochemical assay of p53, nm23, erbB-2, and cathepsin D protein.

BACKGROUND: In view of the cumulative results to date, p53, nm23, erbB-2, and cathepsin D are the most promising investigational prognostic factors in breast cancer. OBJECTIVES: The clinical utility of these molecular markers to predict recurrence was evaluated. METHODS: Archival pathology tissues of 100 breast cancer patients were analyzed by immunohistochemical assay. Molecular biologic data were merged with clinicopathologic variables. RESULTS: Thirty-two patients (32%) had recurrence of disease at a median follow-up of 48 months (range 26-72 months). Investigational factor expression had statistical correlation for recurrence with increasing coexpression: one variable 20.6%, two variables 34.2%, three variables 47.1%, four variables 80.0% (P = 0.003). In univariate analysis, lymph node metastasis, tumor size, erbB-2 protein overexpression, and loss of nm23 protein expression were significant variables to determine recurrence; in multivariate analysis, node status and tumor size emerged as the most significant variables for recurrence. CONCLUSIONS: Coexpression of the studied investigational variables functioned as significant prognostic correlates for recurrence. These findings suggest that the studied investigational prognostic factors possess the ability to discriminate a highly aggressive phenotype in breast cancer.

Biomarkers, Tumor↗
PubMed1997

Distinctive characteristics of germinal center B cells.

A cardinal property of the immune system is its ability to respond to an antigen that was encountered years before with an accelerated and enhanced secondary response. The property of anamnestic reactions depends upon the formation of long-lived compartments of specialized T and B lymphocytes called memory cells. While the origin of the memory T-cell compartment is not known, germinal centers are the specialized sites for memory B-cell generation and the immunoglobulin V-region hypermutation necessary for the affinity maturation of serum antibody. Interestingly, the peripheral differentiation pathway that leads to this most mature B-cell state begins with the recapitulation of many characters of immature B lymphocytes in bone marrow. This review describes the distinctive cellular basis of germinal center reaction and the characteristics of B cells in germinal centers that later enter the memory pool.

Animals↗