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Biomedical subjects

N Yu

Publications and source records attributed to N Yu.

At least 37 records · Page 2Linked to original sources

Comparison of three treatment options for single brain metastasis from lung cancer.

Whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and the combination of both treatment methods were used for the management of single brain metastasis from lung cancer. The purpose of this study is to compare these three different treatment options in terms of local response, survival, and quality of life. From June 1995 to July 1998, 70 lung cancer patients with new diagnosed single brain metastasis were treated with either WBRT alone (n = 29), or SRS alone (n = 23), or the combination of both methods (n = 18). Multiple endpoints, including survival, freedom from local progression (FFLP), freedom from new brain metastasis (FFNBM), local control, Karnofsky performance status (KPS), and causes of death, were measured from the date of treatment completion and compared using univariate and multivariate analyses. For patients treated with WBRT-alone, SRS-alone, and SRS+WBRT, the median survivals were 5.7, 9.3, and 10.6 months, the median FFLP were 4.0, 6.9, and 8.6 months, the median FFNBM were 4.1, 6.7, and 8.6 months, and the local response rates were 55.6, 87.0, and 88.9%, respectively. Four of the 29 patients treated with WBRT-alone continued with progression of disease. The post treatment KPS showed improvement in 41.4, 82.6, and 88.9% of patients treated with WBRT-alone, SRS-alone, and SRS+WBRT, respectively. The progression of new and/or recurred metastatic brain tumor as the cause of death accounted for 51.7%, 50. 0%, and 28.3% of the patients treated with WBRT-alone, SRS-alone, and SRS+WBRT, respectively. Univariate analyses showed that the significant differences among the three treatment arms were observed based on all of the above mentioned endpoints. However, the comparison between SRS-alone and SRS+WBRT groups indicated that adding WBRT only improves FFNBM (P = 0.0392). Cox regression analyses revealed no significant difference in both of the KPS (P = 0.1082) and causes of death (P = 0.081) among the three arms. Both SRS alone and SRS+WBRT seem better in prolonging life and improving quality of life than WBRT alone for patients with single brain metastasis from lung cancer. But the combined therapy did not show significant advantage over SRS alone in improving survival, enhancing local control, and quality of life except for a more favorable FFNBM. Further investigation via a randomized trial is needed to access the value of adding WBRT to SRS in the management of this group of patients. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 37-45 (2000).

Adult↗

Replication rate of feline immunodeficiency virus in astrocytes is envelope dependent: implications for glutamate uptake.

Feline immunodeficiency virus (FIV) induces neurological abnormalities in domestic cats. Previously, we demonstrated that two disparate strains of FIV (FIV-34TF10 and FIV-PPR) varied greatly in the ability to replicate in feline cortical astrocytes. To investigate the impact of the env region on the replication efficiency of these strains, we constructed two env chimera viruses, FIV-34TF10-PPRenv and FIV-PPR-34TF10env, to infect feline cortical astrocytes in vitro. Although all of these viruses infected cortical astrocytes, the efficiency of replication depended on strain, and the env region played an essential role. The viruses containing the env of 34TF10, FIV-34TF10, and FIV-PPR-34TF10env had the greatest replication rate, whereas the viruses containing the env of PPR replicated at a lower level. Other viral regions had modulatory effects on the replication rate, with the FIV-PPR genome providing a slight replication advantage over the FIV-34TF10 genome. We also monitored the effects of these viruses on an important astrocyte function, glutamate uptake; all viruses significantly decreased this activity, but only the viruses containing the env of PPR significantly impaired glutamate uptake without altering the culture viability. These results may be particularly relevant in the context of lentivirus-induced central nervous system disease in which a selective breakdown of astroglial function may contribute to neurodegeneration.

Animals↗

Molecular systematics of pikas (genus Ochotona) inferred from mitochondrial DNA sequences.

The phylogenetic relationships among worldwide species of genus Ochotona were investigated by sequencing mitochondrial cytochrome b and ND4 genes. Parsimony and neighbor-joining analyses of the sequence data yielded congruent results that strongly indicated three major clusters: the shrub-steppe group, the northern group, and the mountain group. The subgeneric classification of Ochotona species needs to be revised because each of the two subgenera in the present classification contains species from the mountain group. To solve this taxonomic problem so that each taxon is monophyletic, i.e. , represents a natural clade, Ochotona could be divided into three subgenera, one for the shrub-steppe species, a second for the northern species, and a third for the mountain species. The inferred tree suggests that the differentiation of this genus in the Palearctic Region was closely related to the gradual uplifting of the Tibet (Qinghai-Xizang) Plateau, as hypothesized previously, and that vicariance might have played a major role in the differentiation of this genus on the Plateau. On the other hand, the North American species, O. princeps, is most likely a dispersal event, which might have happened during the Pliocene through the opening of the Bering Strait. The phylogenetic relationships within the shrub-steppe group are worth noting in that instead of a monophyletic shrub-dwelling group, shrub dwellers and steppe dwellers are intermingled with each other. Moreover, the sequence divergence within the sister taxa of one steppe dweller and one shrub dweller is very low. These findings support the hypothesis that pikas have entered the steppe environment several times and that morphological similarities within steppe dwellers were due to convergent evolution.

Animals↗

Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12.

A novel sequence discovered in a computational screen appears distantly related to the p35 subunit of IL-12. This factor, which we term p19, shows no biological activity by itself; instead, it combines with the p40 subunit of IL-12 to form a novel, biologically active, composite cytokine, which we term IL-23. Activated dendritic cells secrete detectable levels of this complex. IL-23 binds to IL-12R beta 1 but fails to engage IL-12R beta 2; nonetheless, IL-23 activates Stat4 in PHA blast T cells. IL-23 induces strong proliferation of mouse memory (CD4(+)CD45Rb(low)) T cells, a unique activity of IL-23 as IL-12 has no effect on this cell population. Similar to IL-12, human IL-23 stimulates IFN-gamma production and proliferation in PHA blast T cells, as well as in CD45RO (memory) T cells.

Amino Acid Sequence↗

Large-scale DNA-based typing of HLA-A and HLA-B at low resolution is highly accurate specific and reliable.

DNA-based typing of HLA class I alleles of the HLA-A and HLA-B loci using sequence-specific oligonucleotide primers and/or probes has been used for the large-scale typing of individuals for the National Marrow Donor Program unrelated donor registry. Typing was performed by 16 laboratories at a low level of resolution (e.g. A*01, B*07). The results of blinded quality control analysis for the first 12 months of the project show the typing to be highly accurate, specific and reliable. The total error rate based on 11,545 HLA-A and 11,428 HLA-B assignments was 1.1% for HLA-A and 1.9% for HLA-B. This level of accuracy is particularly remarkable because the quality control samples could not be distinguished from 64,180 donor samples tested at the same time by the laboratories.

Bone Marrow Transplantation↗

Dosage of buserelin.

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Administration, Inhalation↗

[Thoracolumbar injuries: pathomorphology of and a new classification].

OBJECTIVE: To introduce a new classification of thoracolumbar injuries. METHODS: Three modes were used to classify the injuries according to the mechanisms of injuries: Type A, flexion-compression fractures; Type B, vertical compression fractures; Type C, distraction injuries. Two groups were used to distinguish the fractures in one type according to the pathomorphological differences and the clinical incidence: Group A, with a more clinical incidence, and Group B, with a less clinical incidence. Three subgroups were used to divide the injuries in one group in consideration of the severity of the fracture instability and the fracture displacement: fracture, subluxation, and dislocation. RESULTS: A new classification of thoracolumbar fractures was established. CONCLUSION: The new classification is more systemic and more convenient.

Humans↗

CD38 signaling in B lymphocytes is controlled by its ectodomain but occurs independently of enzymatically generated ADP-ribose or cyclic ADP-ribose.

CD38 is a type II transmembrane glycoprotein that is expressed by many cell types including lymphocytes. Signaling through CD38 on B lymphocytes can mediate B cell activation, proliferation, and cytokine secretion. Additionally, coligation of CD38 and the B cell Ag receptor can greatly augment B cell Ag receptor responses. Interestingly, the extracellular domain of CD38 catalyzes the conversion of NAD+ into nicotinamide, ADP-ribose (ADPR), and cyclic ADPR (cADPR). cADPR can induce intracellular calcium release in an inositol trisphosphate-independent manner and has been hypothesized to regulate CD38-mediated signaling. We demonstrate that replacement of the cytoplasmic tail and the transmembrane domains of CD38 did not impair CD38 signaling, coreceptor activity, or enzyme activity. In contrast, independent point mutations in the extracellular domain of CD38 dramatically impaired signal transduction. However, no correlation could be found between CD38-mediated signaling and the capacity of CD38 to catalyze an enzyme reaction and produce cADPR, ADPR, and/or nicotinamide. Instead, we propose that CD38 signaling and coreceptor activity in vitro are regulated by conformational changes induced in the extracellular domain upon ligand/substrate binding, rather than on actual turnover or generation of products.

Adenosine Diphosphate Ribose↗

Radiosensitization by intratumoral administration of cisplatin in a sustained-release drug delivery system.

PURPOSE: Effects of combining local irradiation and intratumoral (i.t.) administration of cisplatin (CDDP) in a sustained-release drug delivery system (epi gel) were studied in a murine SCCVII squamous cell carcinoma model in mice. MATERIALS AND METHODS: The epinephrine injectable gel was used as a drug delivery system. Intratumoral pharmacokinetics of CDDP was studied by using 195mPt-CDDP. The tumor volume quadrupling time (TVQT) and tumor growth delay (TGD) time were used to evaluate the antitumor efficacy of treatment regimens. RESULTS: The concentration and residence of 195mPt-CDDP was significantly higher in tumors treated with 195mpt-CDDP/epi gel than in tumors treated with 195mPt CDDP gel or 195mPt-CDDP suspension. Intratumoral administration of CDDP/epi gel (4 mg/kg) produced an average TGD time of 15.5 +/- 2.8 days, which was 5.2 - 7.4 times longer than CDDP suspension i.t. or i.p. When combined with a single dose of radiation (10 Gy), i.t. administration of CDDP/epi gel was 2.0 - 3.6-fold as effective as administered i.t. in suspension (39.2 +/- 4.1 vs. 19.8 +/- 3.9 days of TGD, P < 0.05) or i.p. in solution (39.2 +/- 4.1 vs. 11.0 +/- 1.6 days, P < 0.001) in inhibiting tumor growth and produced 20-60% complete remission of tumors. When combined with fractionated irradiation, pre-irradiation CDDP administration was more effective than post-radiation administration (26.7 vs. 12.1 days of TGD, P < 0.05). Mice treated with CDDP/epi gel i.t. alone or in combination with irradiation, had little systemic toxicity. CONCLUSIONS: Intratumoral administration of CDDP using the sustained-release drug delivery system is an efficient and safe method to maximize the drug concentration in tumor, minimize the systemic toxicity and enhance antitumor efficacy of irradiation.

Animals↗

HLA-Cw*1701 is associated with two sub-Saharan African-derived HLA haplotypes: HLA-B*4201, DRB1*03 and HLA-B*4202 without DRB1*03.

Different extended haplotypes have been described for many ethnic groups, such as African-Americans. The complotype FC(1,90)0 is in linkage disequilibrium with HLA-B42, DRB1*0302 in African-Americans and Southern African Xhosa individuals, suggesting a common ancestry. In order to analyze the distribution of Cw*17 alleles (Cw*1701, 1702) in relation to this African-derived extended haplotype, we studied a large panel of samples from African-American individuals and additionally a group of selected samples carrying HLA-B42, DR3 and HLA-B42, non-DR3 antigens. HLA alleles were assigned using sequence-specific amplification (SSP) and sequence-specific oligonucleotide probe hybridization (SSOP). We have found that all haplotypes (10 in total) carrying the extended haplotypes [HLA-B42, FC(1,90)0, DRB1*0302] were positive for HLA-Cw*1701. Interestingly, HLA B*4201 was found in all samples (17 in total) carrying HLA-B42, DR3, Cw*1701, whereas HLA-B*4202 was found in 10 out of 13 samples from individuals carrying HLA B42, Cw*1701 non-DR3. These findings suggest that HLA-Cw*17 polymorphism is conserved in different ethnic populations and that HLA-B42 alleles seem to separate at least different African-derived haplotypes. The historical context of these findings are important for the study of human evolution and they may be useful for the development of strategies in the search for possible donors in organ transplantation for African-derived populations.

Africa South of the Sahara↗

Development of primordial and prenatal follicles from undifferentiated somatic cells and oocytes in the hamster prenatal ovary in vitro: effect of insulin.

Fetal hamster ovaries were cultured for up to 16 days in the presence or absence of various dosages of insulin to evaluate the induction of folliculogenesis in vitro. In the absence of insulin, a few primordial follicle-like structures appeared by the 4th day, and distinct primary follicles (stage 1) appeared by the 12th day of culture. The organelles in the oocytes and adjacent granulosa cells developed along with follicular growth. Moreover, gap junctions between the oocyte and somatic cell plasma membrane also developed as early as 8 days in culture. In the presence of 0.2 microg/ml insulin, primary follicles developed after 8 days, and approximately 4% secondary follicles with 2-3 layers of granulosa cells appeared after 16 days of culture. However, higher dosages (> 0.2 microg/ml) of insulin retarded primary follicle formation and induced the formation of primordial follicles with larger oocytes. An increased number of larger oocytes with a few granulosa cells accumulated at the periphery of the ovary. The results indicate that although primordial and primary follicles can develop after 12 days in vitro in the absence of exogenous insulin, the latter is required for timely progression of follicular development through primary and secondary stages.

Animals↗

[Clinical value of 99mTc-MIBI imaging, 131I whole body scan and HTG determination for the follow-up of patients with differentiated thyroid carcinoma after 131I therapy].

The purpose of this study was to make a comparative evaluation of 99mTc-MIBI imaging, 131I whole body scan and HTG determination in use for the follow-up of patients with differentiated thyroid carcinoma (DTC) after 131I therapy. Fifty-three patients with DTC had undergone surgical treatment and 131I ablation. Clinical examinations showed that 22 of them had metastases or recurrences. In the follow-up of all the patients, the HTG determination, the 99mTc-MIBI imaging and the 131I-WBS were performed in sequence after the discontinuance of the administration of thyroxin for 4-6 weeks. The results showed that the sensitivity, specificity and accuracy of 99mTc-MIBI imaging were 86.36%, 87.10% and 86.79% respectively; those for HTG were 68.18%, 100% and 86.79% and those for 131I-WBS were 63.64%, 100% and 84.91% respectively. The total sensitivity of the three examinations was 100%; the total specificity and total accuracy were 87.10% and 92.45% respectively. The data of this study suggest that 99mTc-MIBI imaging is a highly sensitive method and the combined use of the three examinations can improve the sensitivity and accuracy of diagnosis for patients with DTC.

Adenocarcinoma↗

[Forty-seven cases of lower respiratory tract infections due to E. ictaluri].

OBJECTIVE: To study the risk factors and treatment of lower respiratory tract infections due to E. ictaluri, and the cause of its improved detection by sputum culture in recent years. METHODS: To sum up the number of positive cultures and analyze the clinical features of the cases with positive sputum culture tested from 1959 to 1998. RESULTS: Before 1996, there were no positive cultures (0%) in 17,500 sputum samples using manual techniques, in 1997 and 1998 the aggregate positive rate was 2.3% (47/1,962), using SCEPTOR detecting instrument. On chi square testing of the two results derived from the two methods, P < 0.001. On drug sensitivity testing, E. ictaluri was sensitive to imipenem, cefotaxime and tobramycin. CONCLUSIONS: E. ictaluri is an uncommon opportunistic pathogen of lower respiratory tract infections. Lowered body resistance is a risk factor, and improved technology is the principal cause for detection of E. ictaluri infections.

Adolescent↗

[The effects of salicylate on noise-induced hearing loss in the guinea pig].

OBJECTIVE: To investigate the effects of salicylate on noise-induced hearing loss (NIHL) in guinea pigs. METHODS: The animals were allocated into four groups (salicylate + noise, saline + noise, noise only and salicylate only) and were exposed to a 4 kHz octave band noise at 105 dB SPL for 2 hours for 5 consecutive days. Dynamic changes of ABR thresholds evoked by clicks were monitored. After physiological examination, the cochleae were processed for the morphological examination by light microscopy. RESULTS: Mean thresholds of ABRs in the experimental group obtained on 5th day of the noise exposure was positively lower than the control groups (P < 0.05). The similar trends of ABR changes were found during other exposure days and after exposure, but the differences were not statistically significant. In the experimental group, there were 37.00 +/- 8.89 hair cell loses as assessed by nucleus staining, and 3.20 +/- 1.07 hair cells with nuclear deformation. The noise group had 74.11 +/- 10.28 hair cell loses and 10.43 +/- 9.71 hair cells with nuclear deformation, whereas the saline group had 63.60 +/- 7.97 hair cell loses and 20.80 +/- 15.48 hair cells with nuclear deformation. The difference between two groups was significant (P < 0.05). CONCLUSION: The results suggest that administration of salicylate facilitates the recovery of cochlear hearing and reduces damage to hair cells after noise exposure.

Animals↗

Topological localization of cysteine 74 in the GABA transporter, GAT1, and its importance in ion binding and permeation.

Xenopus oocytes expressing the GABA transporter GAT1 were exposed to membrane-impermeant sulfhydryl reagents, resulting in decreased GABA transport current, decreased capacitive charge movements, and increased Na+ and Li+ leakage currents. Mutation of cysteine 74 to alanine (C74A) eliminated these effects. The W68S and W68L mutations significantly increased and decreased the transporter's sensitivity, respectively, to sulfhydryl reagents. At each of the positions 73 through 76, cysteine residues were accessible to external MTSET. These findings, together with recent evidence placing the HD2-HD3 loop on the extracellular side, suggest that the HD2 region does not traverse the membrane.

Animals↗

Effects of feline immunodeficiency virus on astrocyte glutamate uptake: implications for lentivirus-induced central nervous system diseases.

Feline immunodeficiency virus (FIV) is a lentivirus of domestic cats that causes a spectrum of diseases remarkably similar to AIDS in HIV-infected humans. As part of this spectrum, both HIV-1 and FIV induce neurologic disorders. Because astrocytes are essential in maintaining the homeostasis of the central nervous system, we analyzed FIV for the ability to infect feline astrocytes. Through immunocytochemistry and reverse transcriptase activity, it was demonstrated that two molecular clones of FIV (FIV-34TF10 and FIV-PPR) produce a chronic low level productive infection of feline astrocyte cultures. To investigate the consequences of this infection, selected astrocyte functions were examined. Infection with FIV-34TF10 significantly decreased the ability of astrocytes to scavenge extracellular glutamate (with a peak inhibition of 74%). The effects of the infection did not appear to be a result of toxicity but rather were more selective in nature because the glucose uptake function of the infected astrocyte cultures was not altered. Our data demonstrate that FIV productively infected, at a low level, feline astrocyte cultures, and as a consequence of this infection, an important astroglial function was altered. These findings suggest that a chronic low grade infection of astrocytes may impair the ability of these cells to maintain homeostasis of the central nervous system that, in turn, may contribute to a neurodegenerative disease process that is often associated with lentivirus infections.

Animals↗

Dynamic regulation of alpha- and beta-chemokine expression in the central nervous system during mouse hepatitis virus-induced demyelinating disease.

Infection of C57BL/6 mice with the V5A13.1 strain of mouse hepatitis virus (MHV-V5A13.1) results in an acute encephalomyelitis and chronic demyelinating disease with features similar to the human demyelinating disease multiple sclerosis. Chemokines are a family of proinflammatory cytokines associated with inflammatory pathology in various diseases. The kinetics and histologic localization of chemokine production in the central nervous system of MHV-infected mice were examined to identify chemokines that contribute to inflammation and demyelination. Transcripts for the chemokines cytokine-response gene-2 (CRG-2), regulated on activation, normal T cell expressed and secreted (RANTES), macrophage-chemoattractant protein-1 and protein-3 (MCP-1, MCP-3), macrophage-inflammatory protein-1beta (MIP-1beta), and MIP-2 were detected in the brains of MHV-infected mice at 3 days postinfection (p.i.), and these transcripts were increased markedly in brains and spinal cords at day 7 p.i., which coincides with the occurrence of acute viral encephalomyelitis. By day 35 p.i., RANTES, CRG-2, and MIP-1beta were detected in brains and spinal cords of mice with chronic demyelination. CRG-2 mRNA expression colocalized with viral RNA and was associated with demyelinating lesions. Astrocytes were the predominant cell type expressing CRG-2 mRNA. These observations suggest a role for chemokines, notably CRG-2, in the initiation and maintenance of an inflammatory response following infection with MHV, which is important in contributing to demyelination.

Animals↗