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Biomedical subjects

G Li

Publications and source records attributed to G Li.

At least 901 records · Page 50Linked to original sources

A numerical study of rapid heating for high temperature radio frequency hyperthermia.

Hyperthermia is a promising adjuvant cancer treatment modality. However, unresolved engineering problems with the production and regulation of temperature distributions within tissues in vivo have frustrated repeated efforts to implement clinical hyperthermia protocols. A major technical problem with hyperthermia production in vivo is the cooling effect caused by circulating blood in larger vessels. Larger blood vessels, when located in heated tumors, can prevent achievement of sufficiently high temperatures, resulting in loss of therapeutic effect. One possible way of circumventing this problem is the delivery of a critical heat dose during a short-term, high-temperature treatment episode to minimize cooling from blood flow. We investigated the concept of such rapid, high-temperature heating of tissue in a two-dimensional finite element numerical model. The model demonstrates the feasibility of interstitial radiofrequency delivery of a therapeutic heat dose, equivalent to 30 min at 43 degrees C, to a 1 cm3 tumor during a 60-s period. The model assumes circulation of cooling fluid through hollow electrodes. A post processor has been designed to display a 3-D image of the temperature distribution, electric field, and thermal dose delivered to a unit volume within the heated tissue.

Blood Circulation↗

[Experimental study of Chinese Agkistrodon acutus venom in activation of rabbit platelets in vivo].

Fourteen Albino rabbits, male and female, were allocated randomly into two groups: control group which had intravenous infusion of normal saline, and experimental group which had intravenous infusion of Chinese Agkistrodon Acutus venom (CAAV) 0.075 mg/kg. Platelet was reduced, plasma PF4 activity and 5-HT concentration increased, 5-HT content in platelets was reduced in the experimental group 10, 20, and 50 minutes after the infusion. It had a significant difference (P < 0.01), compared with that in the control group. Platelets were aggregated into masses under electron microscope 10 minutes after the infusion of CAAV. The study has proved that blood platelets in rabbits are activated by Chinese Agkistrodon Acutus venom.

Agkistrodon↗

[Malignant lymphomas in childhood in Sichuan province--a clinicopathological analysis of 304 cases].

A clinicopathological study of 304 cases of malignant lymphomas (ML) in children in Sichuan province is reported. One hundred and sixty of them were Hodgkin's disease (HD). The ratio between males and females was 5.7 to 1. The disease was more prevalent in children aged from 5 to 9. Cervical lymph nodes were more easily involved. Extra-nodal HD wasn't found in these cases. When subtypes of HD were concerned 62.5% of cases belonged to mixed-cellularity HD. The prognosis of HD was better than that of non-Hodgkin's lymphoma (NHL). The remaining 144 cases were NHL. The ratio between males and females was 3.4 to 1. The disease was more prevalent in children aged from 4 to 14. Eighty four percent of NHL primarily originated from superficial lymph nodes and the other 16.0% of NHL was of extranodal involvement. Seventy two point nine percent of cases in this group was of high grade malignancy. Among them the lymphoblastic type of NHL occupied 44.5%. On the other hand, the follicular type of NHL was rare (0.7%). The specialities of malignant lymphomas in childhood in China are also discussed in the present report.

Adolescent↗

Synergistic induction of thermotolerance in murine natural killer cells by interferon alpha and mild heat shock.

Splenic lymphocytes from C3H/HeN mice were primed in vivo or in vitro with the interferon inducer poly inosine:cytosine (Poly IC) or in vitro with interferon alpha (IFN alpha) and evaluated for their natural killer (NK) activity after exposure to hyperthermia for defined periods. Lytic activity against cells of the NK-susceptible Moloney lymphoma cell line YAC by Poly I:C- or IFN alpha-primed spleen cells exhibited thermotolerance to 41, 42 and 43 degrees C exposure compared to unprimed cells. Spleen cells were also incubated for 1 h at 40 or 37 degrees C prior to exposure to 42 degrees C. Incubation at 40 degrees C produced a modest increase in thermal resistance to 42 degrees C by otherwise unprimed spleen cells. Spleen cells that had been primed by Poly I:C or IFN alpha followed by 1 h at 40 degrees C were rendered even more resistant to hyperthermia at 42 degrees C. These data suggest that two host responses to viral infection, fever and production of IFN alpha, may endow cells involved in the inflammatory response (in this case NK cells) with resistance to more severe stress. Further, IFN alpha and fever may synergize in this protective mechanism.

Animals↗

High frequency of mutator phenotype in human prostatic adenocarcinoma.

Mutator phenotype of nucleotide repeats has been implicated to be involved in human cancer and other diseases. This type of instability may be the direct result of DNA replication and/or repair errors. To examine mutator phenotype during the development of human prostate cancer, we undertook this study to screen 57 patients with prostatic adenocarcinoma for possible mutator phenotype at 18 microsatellite marker loci on 12 chromosomes (3p, 5q, 6p, 7p, 8p, 10q, 11p, 13q, 16q, 17p, 18q and Xq). Overall, in 37 of 57 patients, we have found positive mutator phenotype in at least one of the loci analysed. A significantly greater number of cases were found to be positive for this phenotype among the poorly differentiated than the moderately- and well-differentiated prostatic adenocarcinomas. Our data suggest that mutator phenotype may play an important role in the development and progression of human prostate cancer.

Adenocarcinoma↗

Epidemiology of age-related dementia in China.

The results of these epidemiological studies suggest that the morbidity of age related moderate and severe dementia among the population of 65+ was 1.82%, when adjusted by 1984 US population ratio, it became 3.2%, as reported by US and European authors. Yet MID appears more common than PDD, which was more close to the data from Japan. The average annual incidence of moderate and severe dementia for persons aged 60+ was 0.3% (95% CI: 0.08%-0.52%). The incidence for those aged 70-79 (0.41%) was similar to that reported by US authors (Sluss), 0.58% among 70-74 years old, but lower than that observed by European authors (Hagnell, Magnusso) varied from 1.2% to 5.2% in the same age group. These great differences are likely to be partly due to differences in the age structure of samples, instruments for testing dementia, and diagnostic criteria. The course and outcome of dementia after 3-year follow-up indicated that the average survival time was 8 years, and the risk for death of dementia was 3 times higher than that of the whole cohort; the results were similar to those reported by westerners. The major risk factors for AD as identified in this study showed that family history both in first degree relatives of AD and psychosis were significantly associated with AD. The finding was consistent with the genetic hypothesis in western countries. In 7 risk factors that have been studied in US and European countries, 6 showed that the family history of dementia was significantly associated with AD.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Structure-function relationship of the small GTPase rab5.

Overexpression of rab5 via a Sindbis virus vector resulted in a 2-3-fold stimulation of horseradish peroxidase uptake in BHK-21 cells. Based on this functional assay of rab5 activity, we conducted extensive mutational analysis of the structure-function relationship of rab5. A total of 21 deletion and substitution mutations were created and their effects on rab5 activity were examined. Deletion of the entire C-terminal tetrapeptide motif CCSN abolished rab5 activity. A mutant with the last three residues deleted, however, showed residual rab5 activity. Truncation of only two residues from the C terminus had no effect on the biological activity of rab5. A mutant containing a 4-residue deletion from the N terminus retained full activity in comparison with wild-type rab5. N-terminal deletion of 19 residues only partially blocked rab5 activity. Substitution mutations in the guanine nucleotide binding motifs showed dramatic effects on rab5 function. In addition to the previously reported N133I mutation, the S34N mutation also resulted in a guanine nucleotide binding defective form that was a dominant inhibitor of endogenous rab5 activity. The Q79L mutation (the ras equivalent Q61L decreases intrinsic and GTPase-activating protein-stimulated GTPase activities), however, had no effect on rab5 activity. The S35N mutation, which is immediately downstream of the first GTP/GDP binding motif, decreased guanine nucleotide binding by approximately 4-fold and partially inactivated rab5. Mutations in several other conserved residues (K22A, F57Y, and R81A) also resulted in partial loss of rab5 activity. Eight mutations in and around the putative effector domain had little effect on rab5 activity. In light of these data, the structure-function relationship of rab5 is discussed and compared with that of ras, the prototype of small GTPases.

Amino Acid Sequence↗

The crystal structure and conformational analysis of substituted 2,7-dioxabicyclo[4,1,0]heptanes: 1,2-anhydro-3,4,6-tri-O-benzyl-beta-D-talopyranose.

The title compound, C28H27O5, is triclinic, space group P1 with unit cell dimensions a = 12.763(2), b = 11.130(2), c = 4.764(3) A, alpha = 73.78(3), beta = 82.89(3), gamma = 62.16(1) degrees, V = 574.8(4) A3, and Z = 1. The pyranose ring has an 4H5 conformation with some flattening at C-4. Molecular mechanisms calculations indicate that the 4H5 conformation of the pyranose ring in the title compound is the most stable conformation.

Carbohydrate Conformation↗

Post-translational processing and membrane association of the two early endosome-associated rab GTP-binding proteins (rab4 and rab5).

The two early endosome-associated rab GTP-binding proteins, rab4 and rab5, are suggested to regulate endocytosis. In this report, we examined post-translational processing and membrane association of the two rab proteins. Human rab4 and rab5 were expressed in chicken embryo fibroblasts using a Sindbis virus expression vector. Cells were labeled with either [35S]methionine or [3H]mevalonolactone. Cell lysates were immunoprecipitated with antisera specific for rab4 and rab5, respectively, and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It was found that both rab4 and rab5 contained at least three forms: the precursor form, the isoprenylated intermediate, and the isoprenylated mature form of faster mobility. The rab5 intermediate comigrated with the precursor form, whereas the rab4 intermediate migrated slightly faster than the precursor form. The intermediate form of rab4, but not rab5, accumulated in the presence of a chymotrypsin-like protease inhibitor (N-acetyl Tyr ethyl ester), suggesting that proteolysis was required for generation of the mature form. Furthermore, the intermediate and mature forms of rab4, but not rab5, were carboxyl-methylated as demonstrated by incorporation of alkali-labile counts from [methyl-3H]methionine. Membrane association of the distinct rab4 and rab5 forms was examined by subcellular fractionation and Triton X-114 partitioning. The precursor forms were found in the cytosol and partitioned into the aqueous phase. The mature forms were membrane-associated and partitioned into the detergent phase. Unexpectedly, the isoprenylated intermediate forms of both rab4 and rab5 partitioned exclusively into the aqueous phase. Taken together, the data indicate that the entire post-translational processing, which includes isoprenylation, carboxyl methylation (rab4), and possibly proteolysis, confers the competency for membrane association of rab4 and rab5.

Animals↗

Stimulation of insulin release from permeabilized HIT-T15 cells by a synthetic peptide corresponding to the effector domain of the small GTP-binding protein rab3.

A synthetic peptide (rab3AL) corresponding to the effector domain of rab3, a small GTP-binding protein, stimulated basal and potentiated Ca(2+)- as well as GTP gamma S-evoked insulin secretion about 2-fold from streptolysin-O permeabilized HIT cells. This effect was specific, since the analogous peptides of ras or rab1 did not affect the exocytotic event. The more than additive effect of rab3AL on Ca2+ or GTP gamma S stimulation indicates a distinct mode of action of the peptide. The partial loss of cytosolic proteins from permeabilized cells was accompanied by a faster run-down of the secretory response to Ca2+ than the one to GTP gamma S. The persistent effect of rab3AL under these conditions points to a membrane localization of its target. These results suggest that rab3 and its effector are involved in the regulation of insulin secretion.

Calcium↗

Blockade of mevalonate production by lovastatin attenuates bombesin and vasopressin potentiation of nutrient-induced insulin secretion in HIT-T15 cells. Probable involvement of small GTP-binding proteins.

Small G-proteins (SMGs) require isoprenylation for their association with membranes. We have examined protein isoprenylation, subcellular distribution of SMGs, cytosolic Ca2+ changes and insulin secretion in HIT-T15 cells after treatment with lovastatin, which inhibits the production of isoprenoids by blocking mevalonate production by 3-hydroxy-3-methylglutaryl-CoA reductase. Numerous proteins in the 20-70 kDa range were found to be isoprenylated. Most of these proteins co-migrated with SMGs (21-27 kDa). Lovastatin treatment (25 microM, 24 h) decreased protein isoprenylation and affected the distribution of several SMGs, causing a large accumulation in the cytosol and a detectable decrease in membranes. Lovastatin selectively attenuated the potentiating action of bombesin and vasopressin, which activate phospholipase C in these cells, on insulin secretion stimulated by nutrients (glucose + leucine + glutamine). This lovastatin effect was overcome by mevalonate. Insulin secretion stimulated by nutrients alone or insulin release in the presence of the potentiating agents forskolin or phorbol myristate acetate remained unaffected. As the modulation of insulin secretion by isoprenaline and somatostatin were not altered by lovastatin, the drug does not non-selectively affect the binding of ligands to their receptors. Lovastatin did not interfere with the activation of phospholipase C by bombesin and vasopressin, since the rise in cytosolic Ca2+ induced by these agents was not changed. Limonene, proposed to block specifically prenyl-protein transferases of SMGs, did not alter protein isoprenylation patterns, but inhibited the stimulated insulin secretion. In conclusion, lovastatin selectively attenuated the potentiation of nutrient-induced insulin secretion by bombesin and vasopressin without affecting their activation of phospholipase C. The concomitant changes in SMG isoprenylation and their subcellular distribution after lovastatin treatment suggest that SMGs could play an important role in the bombesin and vasopressin action on insulin secretion.

Animals↗