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Biomedical subjects

M Yu

Publications and source records attributed to M Yu.

At least 307 records · Page 17Linked to original sources
PubMed1995

High numbers of autoantigen-reactive mononuclear cells expressing interferon-gamma (IFN-gamma), IL-4 and transforming growth factor-beta (TGF-beta) are present in cord blood.

Umbilical cord blood of neonates and peripheral blood of healthy adults were analysed by in situ hybridization for numbers of mononuclear cells (MNC) expressing the cytokines IFN-gamma, TGF-beta and IL-4 mRNA without culture and after culture in the presence of acetylcholine receptor (AChR), myelin basic protein (MBP) and peripheral myelin protein P2. These antigens were chosen since they represent autoantigens in putatively immune-mediated neurological diseases. The numbers of cells expressing cytokine mRNA after 72 h culture in the presence of AChR, MBP and P2 were higher in cord blood than in peripheral blood of healthy adults. IFN-gamma, TGF-beta and IL-4 were always elevated in parallel. In cord blood there was a pronounced reactivity to several of the tested antigens, while such broad reactivity was not found in peripheral blood of healthy adults. No differences in cytokine mRNA expression were found between cord blood and peripheral blood of adults when cells were analysed without culture. The results show a capacity of cord blood cells to react to several autoantigens by the up-regulation of cytokine mRNA expression.

Adult↗
PubMed1995

Assessment of capacity to comply with medication regimens in older patients.

OBJECTIVE: To develop an instrument that will facilitate and focus the assessment of a patient's capacity to adhere to a medication regimen before its initiation. DESIGN: This is a crossectional study that compares medical inpatients and outpatients to an age-matched, community-living, independent and relatively healthy group on their ability to adequately understand and implement hypothetical but realistic medication regimens. SETTING: Department of Veterans Affairs Medical Center, Sepulveda, California. PARTICIPANTS: Fifty-five older subjects (65 years or older) were divided into three groups: (1) generally healthy comparisons (standard group) (n = 20); (2) medical outpatients (n = 15); and (3) medical inpatients ready for discharge (n = 20). MEASUREMENTS: Older subjects were first tested on their capacity to comply with a difficult medication regimen presented in scenario form. If scores on the first scenario did not meet a standard group-derived cutoff point, further testing was conducted with a simpler scenario to identify greater levels of impairment. RESULTS: The outpatient group had significantly lower scenario scores than did the healthy comparison group (P < .03). The simpler scenario also showed a trend toward outpatient impairment (P = .06). In the comparison group, only 5% failed Scenario 1, and none failed Scenario 2. The outpatient group had the most difficulty, with 40% failing Scenario 1 and one-third of those failing Scenario 2. This differed significantly from the comparison groups (Fisher's Exact P < .03). In the inpatient group 20% failed Scenario 1 and 75% of those failing Scenario 2. The sensitivity and specificity of the Folstein Mini-Mental State Examination in identifying scenario-impaired subjects were 73% and 80%, respectively. Question types were analyzed to determine which questions were most frequently missed. Memory and judgment questions were found overall to be the most frequently missed. Healthy controls missed some judgment questions; however, the outpatient group was significantly worse in this category (chi 2 = 5.08; P = .01). All three groups improved their scenario performance significantly with question cueing. CONCLUSION: A significant number of medically ill outpatients encountered difficulty in understanding or remembering correctly hypothetical but realistic medication regimens. This suggests that an older medical patient's cognitive and functional capacity to comply with medication regimens of differing complexity can be specifically assessed before the start of the regimen and probably should be assessed in patients whose compliance capacity is in question. The assessment instrument under development in this study may be helpful in detecting those who need assistance with medications, thus identifying the need for intervention before poor compliance can lead to increased morbidity, rehospitalization, and increased medical costs.

Age Factors↗
PubMed1995

Differential expression of 11 beta-hydroxysteroid dehydrogenase 1 and 2 in the developing ovine fetal liver and kidney.

In adult mammals, liver and kidney are the two major sites of biosynthesis for 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) 1 and 2 respectively. In the present study, the expression of these two isozymes in the developing ovine fetal liver and kidney was characterized. Livers and kidneys were obtained from fetal sheep at days 85, 100-120 and 140-143 of gestation (term = 145 days). Tissue levels of 11 beta-HSD2 mRNA were assessed by Northern blot analysis. 11 beta-HSD dehydrogenase and reductase activities in tissue homogenates were determined by a radiometric conversion assay using cortisol and cortisone as physiological substrates respectively. The unidirectional 11 beta-HSD2 dehydrogenase activity was identified by its distinct cofactor preference (NAD), and by its unique ability to metabolize dexamethasone (Dex). In the liver, 11 beta-HSD1 dehydrogenase and reductase activities were present by day 85, and their levels did not change between days 85 and 100-120 but increased more than twofold at days 140-143. This was consistent with changes we reported previously in the fetal hepatic 11 beta-HSD1 mRNA. 11 beta-HSD1 reductase activity was always higher than the dehydrogenase activity. 11 beta-HSD2 mRNA and activity were undetectable in the fetal liver at all three ages. By contrast, 11 beta-HSD2 mRNA was present in the fetal kidney by day 85, and its abundance increased progressively thereafter. There was a parallel increase in the renal 11 beta-HSD2 activity. Dex was also converted to 11-dehydro-Dex by the fetal kidney. In keeping with the absence of the full-length 11 beta-HSD1 mRNA, 11 beta-HSD1 activity was undetectable in the kidney. These results indicate that (1) 11 beta-HSD1 and 2 genes are differentially expressed and regulated in the fetal liver and kidney during development, (2) since the hepatic 11 beta-HSD1 reductase activity is always higher than the dehydrogenase activity, the fetal liver may be a potential extra-adrenal source of cortisol, and (3) 11 beta-HSD2 in the kidney may play a very important role in protecting the fetus from elevated levels of bioactive glucocorticoids.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Determinant-regulated onset of experimental autoimmune encephalomyelitis: distinct epitopes of myelin proteolipid protein mediate either acute or delayed disease in SJL/J mice.

In the present study we address the question of whether distinct self-determinants can target alternative autoimmune disease patterns in experimental autoimmune encephalomyelitis (EAE), an animal model widely used for studying multiple sclerosis. We have found that the clinical course of EAE can be determined by the target peptide selected for induction of disease. In SJL/J mice, actively induced and passively transferred EAE mediated by the immunodominant PLP determinants p139-151 and p178-191 consistently produced a rapid onset of severe clinical signs. In contrast, a delayed onset of both active and passive EAE is associated with the nondominant cryptic PLP determinant p104-117. The delayed disease induced with p104-117 is not associated with any unusual peptide feature, with bystander immunoregulation, with inept class II MHC binding, or with failure to induce T cell expression of CD44, VLA-4, or IL-2 receptor upon activation. However, delayed disease is associated with innate qualities of the T cell repertoire responding to the p104-117 determinant. T cell lines responding to the cryptic p104-117 show limited TCR-V beta utilization compared to the diverse repertoire responding to the dominant p139-151 determinant. The repertoire deletions are accompanied by low level production of pathogenic Th1 cytokines (IFN gamma; IL-2) and increased production of regulatory Th2 (IL-4) cytokine in activated p104-117 primed T cells. Thus, the delayed encephalitogenicity of p104-117 may be due to TCR-V beta deletions and activation defects in the responding T cell repertoire. The development of "slow disease" mediated by autoreactivity against hidden self-determinants may have important implications in the pathogenesis of both relapsing and chronic autoimmune demyelinating disease.

Acute Disease↗
PubMed1995

Positive selection of CD34+ hematopoietic cells using an immunoaffinity column results in T cell-depletion equivalent to elutriation.

Acute graft-vs.-host disease (GVHD) continues to present a barrier to successful allogeneic marrow transplantation. T cell-depletion may prevent severe GVHD but carries an increased risk of graft rejection and relapse posttransplant. Clinical trials have defined the number of lymphocytes associated with sustained engraftment but low risk of significant GVHD (greater than grade I or II skin only) as < or = 10(5)/kg. We examined T cell-depletion resulting from positive selection of CD34+ hematopoietic cells with a biotinylated monoclonal anti-CD34 antibody and an immunoaffinity column. Eleven patients (six myeloma and five breast cancer) underwent both peripheral blood stem cell (PBSC) collection and marrow harvest prior to autologous transplantation. One PBSC collection and one-third of each marrow underwent column separation. PBSCs were enriched for CD34+ cells from an initial mean of 1.5 to 53.3%, while marrow went from an initial mean of 2.8 to 65.4%. PBSC were depleted of CD3+ cells from an initial mean of 9.6 x 10(9) to 8.6 x 10(6). Marrow CD3+ lymphocyte content was reduced from an initial mean of 5.6 x 10(9) to 8 x 10(5). Since the column permits quantification and salvage of depleted T cells, its use should allow re-addition of T cell-aliquots associated with minimal risk for GVHD and rejection. In addition, since PBSCs were as readily depleted as marrow, allogeneic PBSC transplant may be feasible using this method.

Antigens, CD↗
PubMed1995

Intravesical instillation of interleukin-2. An effective method for preventing the recurrence of bladder cancer.

The result of intravesical instillation with interleukin-2 (IL-2) for preventing the recurrence of bladder cancer and discussion of its mechanism was reported. 20 patients with histologically confirmed bladder transitional cell carcinoma were investigated. 2,000 u IL-2 was intravesically instillated every day for six days after resection of the neoplasm. The serum level of tumor necrosis factor (TNF) was significantly increased in 17 patients after IL-2 therapy. Recurrence occurred in 4 patients during the follow-up period of 10-18 months. The basic level of serum TNF was low and was not increased or even decreased after IL-2 in these patients. On the contrary, recurrence did not occur in another 5 patients with low basic level of TNF, but it was significantly increased after treatment of IL-2. TNF played a key role in preventing the recurrence of bladder cancer. The patients who had low basic level of TNF, which did not markedly increase or even decrease after IL-2 therapy were at high risk of recurrence.

Administration, Intravesical↗
PubMed1995

Induction of atypical hyperplasia, apoptosis, and type II estrogen-binding sites in the ventral prostates of Noble rats treated with testosterone and pharmacologic doses of estradiol-17 beta.

BACKGROUND: We have previously shown that combined administration of testosterone (T) and a low dose of estradiol 17 beta (T+LDE2) for 16 weeks induces an atypical proliferative lesion, termed dysplasia, in the dorsolateral prostates of intact Noble rats (1, 2). The lesion was accompanied by increases in the levels of a moderate affinity, high capacity, estrogen-binding site (type II sites) found exclusively in dorsolateral prostates of these animals (1, 3). In contrast, a proliferative response and type II sites were not observed in the ventral prostates (VP) of the same rats treated with this hormonal regimen. In the current study, rats were treated with a higher dose of E2 (4 x LDE2) but the same dose of T (T+HDE2) for 16 weeks. Our aims were to determine how the VP would respond to the T+HDE2 treatment. EXPERIMENTAL DESIGN: Intact Noble rats were treated with T+HDE2 for 16 weeks. Prostatic tissues were removed for histology, electronmicroscopy, and type II site measurements. Proliferating cells were identified by the histochemical detection of proliferating cell nuclear antigen and colcemid-arrested mitotic figures. Apoptotic cells were recognized by their characteristic histologic and ultrastructural features and by in situ detection of nuclear DNA fragmentation. Data were compared with results previously obtained from VP of rats treated with T+LDE2. RESULTS: The VP of T+HDE2-treated animals contained focal atypical hyperplasia and wide-spread apoptosis. Proliferating cell nuclear Ag-positive-stained epithelial cells and mitotic figures were only present in foci of atypical hyperplasia. Total DNA content of the VP was significantly increased, but the tissue wet weight was not augmented. Nuclear type II sites, never observed in untreated or T+LDE2-treated rats, were detected in the VP of the majority of T+HDE2-treated animals. CONCLUSIONS: The administration of a high dose of E2 with T produced a unique lesion in the VP, characterized by simultaneous occurrence of apoptosis and proliferation. The synergy between androgens and estrogens, via type II site induction, likely produces the proliferative response. On the other hand, inhibition of intracellular androgen activation pathways, leading to reduction in cell survival factors, may be the cause for the apoptotic development. Our model, thus, provides a unique opportunity to further study the balance/switch between cell proliferation and apoptosis that is often disturbed during cancer development.

Animals↗
PubMed1995

Increased titer of recombinant AAV vectors by gene transfer with adenovirus coupled to DNA-polylysine complexes.

One of the principal problems with using recombinant adeno-associated virus vectors (rAAV) as vehicles for gene delivery has been the difficulty in obtaining high-titer virus stocks after the initial transfection into producer cells. In this report we describe a method for transfecting cells at extremely high efficiency with rAAV vector DNA and complementation plasmid while simultaneously infecting those cells with replication competent adenovirus using adenovirus-polylysine-DNA complexes. We further show that this technique results in an increase in rAAV transducing titer by two orders of magnitude over what is typically achieved by standard calcium phosphate transfection.

Adenoviridae↗
PubMed1995

[Abnormal expression and clinical significance of mutation p53 gene on human bladder cancer].

In order to study the relationships between the mutant p53 gene and human bladder cancer, the authors used in situ hybridization to detect 30 of bladder cancer and 4 of normal bladder samples. The results showed that p53 gene positive rate of mRNA was 23.3% in cancer patient, and all negative in normal-bladder. The positive rate was significantly different in pathological grading and clinical stages of carcinoma (P < 0.05). It suggests that the mutant p53 gene participats in transformation of carcinoma and may be used as a tumor marker for determinating invasiveness and prognosis of bladder carcinoma.

Carcinoma, Transitional Cell↗
PubMed1995

[Influence of radiotherapy and chemotherapy on the function of malignant tumor patients and regulation function of acupuncture].

The observation on the indexes of cortisol, estradiol, estriol and testosterone showed that incretory function of malignant tumor patients had different extent of pathologic changes, after radiotherapy and chemotherapy, making the change strengthened. Acupuncture can regularize this disorder of incretory function of patients treated with radiotherapy and chemotherapy to some extent.

Acupuncture Therapy↗
PubMed1995

[IgG RF analysis of supernatant of cultured synovia in patients with rheumatoid arthritis].

We used Enzyme Linked Immuno-Sorbent Assay (ELISA) to measure IgG RF of supernatant of cultured knee synovia in 45 patients with various rheumatic diseases (Harvest time for the supernatant was 1,4,7,14,28 days). 25 cases of patients with osteoarthritis (OA) and non-synovitis (Non-S) were regarded as the negative control. IgG RF was positive in 4 of 12 patients with rheumatoid arthritis (RA), whose IL-1 bioactivity is also high. Meanwhile these 4 patients had not received disease-modifying anti-rheumatic drugs (DMARDs) and their clinical and laboratory parameters were active. IgG RF was negative in other groups. It is suggested that humoral factor such as IgG RF and cytokine such as IL-1 may play the synergistic role in the pathogenesis of RA and DMARDs may suppress these two kinds of pathological factors.

Adult↗
PubMed1995

[The course of malaria control and present status in Zhejiang Province].

Through forty years' sustained efforts in the prevention and treatment of malaria in Zhejiang Province, the malaria incidence dropped from 76.650/000 in the Fifties to 0.910/000 in the Eighties. Three malaria epidemics emerged in 1954, 1962 and 1973, respectively, among them the epidemic in 1962 was the most serious one with 0.88 million cases reported and an incidence of 3300/000. The annual incidence of the overall counties/cities was below 10/000 after 1988. Only 172 malaria cases were found in 1992, the incidence being 0.040/000. No indigenous malaria case was found in 38 counties in 1992, accounting to 43.7% of the total malaria endemic counties. The number of imported malara cases was 3,829, amounting to 89.2% of the total number of cases. Through the spot-check of the Ministry of Public Health in 1993, it was confirmed that the criteria of basic elimination of malaria in the province was attained.

Animals↗
PubMed1995

[Increased expression of platelet-derived growth factor beta receptor gene in hypoxic rat lungs].

The changes of platelet-derived growth factor (PDGF) beta receptor gene expression in hypoxic rats lungs was examined. Northern blots analysis revealed that normal lungs expression PDGF-beta receptor mRNA, with the longer of hypoxia the level of the mRNA increased rapidly. It reached a maximum at day 4, and was 1.34 fold as compared with the control (P < 0.05). Immunohistochemistry investigation showed that PDGF-beta receptor mainly distributed on smooth muscle cells and endothelial cells of middle and small arterial trees in rat lung. With hypoxia, the distribution of PDGF-beta receptors did not change, but it was more intense and reached a maximum at day 7, and was 2.40 fold as compared with the control (P < 0.05). The results suggested that increased expression of PDGF receptor gene may play a role in hypoxic pulmonary vascular remodeling.

Animals↗
PubMed1995

[A clinical analysis of 93 cases with corticosteroid cataract].

According to the classical diagnostic criteria, the characteristics of 93 cases (182 eyes) of corticosteroid cataract (CSC) were investigated to analyze the relationship between its lens opacity and each of the following items: the duration, total amount of corticosteroid used, visual acuity and glaucoma. Posterior capsular lens opacity can be found in a sensitive patient after four months of administration of corticosteroid. Juvenile and male patients are vulnerable to the disease. Particularly, the variation of III-grade lens opacity is much closely related to the duration and total amount of corticosteroid used. 83.8% of patients were accompanied by glaucoma which may be the main cause of visual impairment of I and II grade lens opacity. The authors propose that CSC be divided into four grades according to the distribution and degree of the lens opacity. It should be alert that CSC might be accompanied by glaucoma.

Administration, Topical↗
PubMed1994

Activity and cleavage site specificity of an anti-HIV-1 hairpin ribozyme in human T cells.

Human CD4+ T cells (Molt-4) were transduced with retroviral vectors containing a hairpin ribozyme which targets the rev/env coding region of HIV-1 RNA (HXB2: 8629-8644). This target sequence is conserved among many HIV-1 clones, including the prototype virus HXB2, but the infectious clone SF2 contains a single nucleotide substitution at the cleavage site (from N*GUC to N*UUC). Cells stably expressing the ribozyme or its disabled counterpart were challenged with HXB2 or SF2 and the amount of p24 antigen produced was monitored. While this ribozyme was effective in inhibiting the replication of HXB2 in Molt 4 cells, it showed only marginal inhibitory effect on SF2 replication. The same level of virus production was observed with cells transduced by the disabled ribozyme, which functions essentially as an antisense molecule. Expression of the ribozyme was comparable in HXB2- or SF2-infected cells as detected by reverse transcription-polymerase chain reaction. These data provide in vivo evidence that the antiviral activity of the hairpin ribozyme is strictly dependent on the presence of the cleavage site in the target RNA and supports the conclusion that the ribozyme acts as catalytic RNA rather than as antisense RNA in vivo.

Base Sequence↗