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Biomedical subjects

W He

Publications and source records attributed to W He.

At least 181 records · Page 10Linked to original sources

[Kidney reinforcing and yang supporting action of cistanche deserticola Y. C. Ma before and after preparation].

The weights of seminal vesicle and prostate gland of castrated young rats were significantly increased by administration of alcoholsoluble extract from decoction of Cistanche deserticola. The weights of testes, seminal vesicle and prostate gland in mice and rats were also increased by the extract. The phagocytic function of intra-abdominal macrophage in mice was activated by decoction of Cistanche deserticola. The results showed no statistical differences between crude and prepared drugs. The maximum oral tolerance for mouse was 40 g/kg.

Animals↗

Distinct modes of interaction of SHC and insulin receptor substrate-1 with the insulin receptor NPEY region via non-SH2 domains.

Insulin receptor substrate 1 (IRS-1) and src homology and collagen protein (SHC) are signaling proteins which are rapidly phosphorylated on tyrosines after insulin receptor (IR) activation. We have recently shown that both SHC and IRS-1 interact with the tyrosine-phosphorylated NPEY motif of the IR and insulin-like growth factor I receptor via non-SH2 domains (Gustafson, T. A., He, W., Craparo, A., Schaub, C. D., and O'Neill, T. J. (1995) Mol. Cell. Biol. 15, 2500-2508; O'Neill, T. J., Craparo, A., and Gustafson, T. A. (1994) Mol. Cell. Biol. 14, 6433-6442; Craparo, A., O'Neill, T. J., and Gustafson, T. A. (1995) J. Biol. Chem. 270, 15639-15643). In this study we characterize these interactions by examining the effects of 18 amino acid substitutions within and around the IR NPEY motif upon interaction with SHC and IRS-1. We confirm that Tyr-960 within the NPEY motif of the IR is essential for both IRS-1 and SHC interaction and that Asn-957 and Pro-958 are essential for IRS-1 interaction and important but not critical for SHC interaction. Additional mutations surrounding the NPEY motif revealed completely distinct patterns of interaction for SHC and IRS-1. Specifically, mutation of Leu-952 or Tyr-953 (at positions -7 and -8 from Tyr-960) markedly reduced IRS-1 interaction but had no effect upon SHC interaction. Likewise, mutation of Ala-963 (+3) reduced IRS-1 but not SHC interaction. Conversely, substitution of Leu-961 (+1) with either Ala or Arg reduced SHC interaction by 70 and 90%, respectively, yet had no effect upon interaction with IRS-1. Our data show that the sequences within and surrounding the NPEY contribute differentially to either SHC or IRS-1 recognition. Our findings suggest mechanisms by which the differential interaction of known receptors with IRS-1 and SHC may be mediated.

Amino Acid Sequence↗

Induction of TCR-gamma delta expression on triple-negative (CD3-4-8-) human thymocytes. Comparative analysis of the effects of IL-4 and IL-7.

It is well established that IL-4 and IL-7 control the differentiation of TCR-gamma delta-expressing cells from CD3/TCR-negative thymic precursors. In this study, we have compared the in situ expression of IL-4 and IL-7 mRNA in human postnatal thymus with the in vitro effect of IL-4 and IL-7 on the expansion of TCR-gamma delta + cells from highly purified CD3-4-8- triple-negative thymocytes. IL-4 mRNA expression was restricted to subcapsular regions of the human thymus, whereas cells expressing IL-7 mRNA were distributed throughout the thymic tissue, with some enrichment in subcapsular and cortical regions. Epithelial cells of the outer layer of Hassall's corpuscle strongly expressed IL-7 mRNA. IL-7 but not IL-4 or IL-2, stimulated strong proliferative activity and cellular expansion of triple-negative thymocytes. All three induced the appearance of TCR-gamma delta + cells within 4 days of culture. In the presence of IL-4 or IL-2, 30 to 55% of viable cells were TCR-gamma delta + after 5 to 9 days, whereas only 10 to 15% triple-negative thymocytes cultured with IL-7 expressed TCR-gamma delta. However, comparable absolute numbers of viable TCR-gamma delta + thymocytes were recovered when triple-negative thymocytes were cultured with IL-4 or IL-7, but not with IL-2. Taken together, our results suggest that IL-4 and IL-7 (both of which are produced in situ in thymic tissue) play equally important roles in the in vitro generation of TCR-gamma delta + thymocytes from triple-negative precursor cells.

Gene Expression↗

A randomized trial of three antipneumocystis agents in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group.

BACKGROUND: We evaluated the effectiveness of three treatment strategies for the prevention of a first episode of Pneumocystis carinii pneumonia in patients infected with the human immunodeficiency virus (HIV). METHODS: In an open-label trial, 843 patients with HIV infection and fewer than 200 CD4+ cells per cubic millimeter received zidovudine plus one of three randomly assigned prophylactic agents, beginning with trimethoprim-sulfamethoxazole, dapsone, or aerosolized pentamidine and followed by a defined sequence of other drugs to be used in cases of intolerance. RESULTS: The estimated 36-month cumulative risks of P. carinii pneumonia were 18 percent, 17 percent, and 21 percent in the trimethoprim-sulfamethoxazole, dapsone, and aerosolized-pentamidine groups, respectively (P = 0.22). The difference in risk among treatment strategies was negligible in patients entering the study with 100 or more CD4+ lymphocytes per cubic millimeter. In those entering with fewer than 100 CD4+ cells per cubic millimeter, the risk was 33 percent with aerosolized pentamidine, as compared with 19 percent with trimethoprim-sulfamethoxazole and 22 percent with dapsone (P = 0.04). The lowest failure rates occurred in patients receiving trimethoprim-sulfamethoxazole, and failures were more common with 50 mg of dapsone than with 100 mg. Toxoplasmosis developed in less than 3 percent of patients. Of the patients assigned to the two systemic therapies, only 23 percent were receiving their assigned drug and dose when they completed the study. The median survival was approximately 39 months in all three groups, and the mortality attributable to P. carinii pneumonia was only 1 percent. CONCLUSIONS: In patients with advanced HIV infection, the three treatment strategies we examined have similar effectiveness in preventing P. carinii pneumonia. Strategies that start with trimethoprim-sulfamethoxazole or with high-dose dapsone, rather than aerosolized pentamidine, are superior in patients with fewer than 100 CD4+ lymphocytes per cubic millimeter.

AIDS-Related Opportunistic Infections↗

A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group.

BACKGROUND: Cryptococcal meningitis and other serious fungal infections are common complications in patients infected with the human immunodeficiency virus (HIV). Fluconazole is effective for long-term suppression of many fungal infections, but its effectiveness as primary prophylaxis had not been adequately evaluated. METHODS: We conducted a prospective, randomized trial that compared fluconazole (200 mg per day) with clotrimazole troches (10 mg taken five times daily) in patients who were also participating in a randomized trial of primary prophylaxis for Pneumocystis carinii pneumonia. RESULTS: After a median follow-up of 35 months, invasive fungal infections had developed in 4.1 percent of the patients in the fluconazole group (9 of 217) and in 10.9 percent of those in the clotrimazole group (23 of 211; relative hazard, as adjusted for the CD4+ count, 3.3; 95 percent confidence interval, 1.5 to 7.6). Of the 32 invasive fungal infections, 17 were cryptococcosis (2 in the fluconazole group and 15 in the clotrimazole group; adjusted relative hazard, 8.5; 95 percent confidence interval, 1.9 to 37.6). The benefit of fluconazole was greater for the patients with 50 or fewer CD4+ cells per cubic millimeter than for the patients with higher counts. Fluconazole was also effective in preventing esophageal candidiasis (adjusted relative hazard, 5.8; 95 percent confidence interval, 1.7 to 20.0; P = 0.004) and confirmed and presumed oropharyngeal candidiasis (5.7 and 38.1 cases per 100 years of follow-up in the fluconazole and clotrimazole groups, respectively; P < 0.001). Survival was similar in the two groups. CONCLUSIONS: Fluconazole taken prophylactically reduces the frequency of cryptococcosis, esophageal candidiasis, and superficial fungal infections in HIV-infected patients, especially those with 50 or fewer CD4+ lymphocytes per cubic millimeter, but the drug does not reduce overall mortality.

AIDS-Related Opportunistic Infections↗

Amino acid sequence of rat kidney glutathione synthetase.

Glutathione (GSH) synthetase [gamma-L-glutamyl-L-cysteine:glycine ligase (ADP-forming), EC 6.3.2.3], an enzyme present in almost all cells, catalyzes the ATP-dependent synthesis of GSH from gamma-L-glutamyl-L-cysteine and glycine. Highly purified preparations of the enzyme have been obtained from rat kidney and several lower forms. The rat kidney enzyme (M(r), 118,000), which contains approximately 2% carbohydrate, is composed of two apparently identical subunits. The cDNA encoding rat kidney GSH synthetase was isolated from a rat kidney lambda gt11 cDNA library by immunoscreening with an antibody prepared against the isolated enzyme. The cDNA contains 1905 nucleotides and an open reading frame of 1422 nucleotides coding for 474 amino acids. The cDNA has a 3' untranslated region of 439 nucleotides, which includes a poly(A) tail. The deduced amino acid sequence (M(r), 52,344) contains all five of the peptide sequences that were independently determined by Edman degradation. The cDNA was expressed in Escherichia coli. The amino acid sequence of the rat kidney enzyme has no significant similarity to that of the enzyme from E. coli and shows some similarity to those deduced for the yeast and frog enzymes. Knowledge of this amino acid sequence is expected to facilitate elucidation of the sequence of the corresponding human enzyme and to lead to studies on the biochemical mechanisms involved in human GSH synthetase deficiency as well as to development of improved methods for prenatal diagnosis of these inborn diseases.

Amino Acid Sequence↗

Elevated plasma chitotriosidase activity in various lysosomal storage disorders.

Recently a striking elevation of the activity of chitotriosidase, an endo beta-glucosaminidase distinct from lysozyme, was found in plasma from patients with Gaucher type I disease (McKusick 230800). Plasma chitotriosidase originates from activated macrophages and this elevation is secondary to the basic defect in Gaucher disease. To investigate the specificity of this phenomenon, we have investigated 24 different lysosomal storage diseases. In 11 different diseases increased chitotriosidase activity in plasma was found (in 28% of the patients). None of these diseases showed elevations as high as in Gaucher disease. Chitotriosidase was not significantly elevated in plasma from 20 different non-lysosomal enzymopathies or in plasma from patients with infectious diseases associated with hepatomegaly. The results show that marked elevation of chitotriosidase activity in plasma appears to be specific for Gaucher disease. The data further suggest that elevated levels of chitotriosidase activity in plasma from patients with unexplained diseases may be indicative for a lysosomal disorder.

Adult↗

Differential effects of interleukin-2 and interleukin-7 on the induction of CD4 and CD8 expression by double-negative human thymocytes.

Expression of cell surface CD4 (in the absence of CD3/T cell receptor) characterizes an early stage of intrathymic T cell development. Here, we investigated the appearance of CD4 and CD8 expression on highly purified CD4-8- double-negative human thymocytes in response to interleukin (IL)-7 and IL-2. While IL-7 preferentially promoted the appearance of CD4 single-positive and CD4+8+ double-positive thymocytes, IL-2 primarily induced CD8 single-positive thymocytes. A significant fraction of CD4 single-positive cells generated from double-negative thymocytes via IL-7 lacked cell surface CD3 expression. In contrast, the majority of CD8 single-positive cells generated from double-negative thymocytes via IL-2 coexpressed CD3. We conclude that IL-7 and IL-2 exert differential effects on the differentiation of early human T cell progenitors.

CD3 Complex↗

Phosphotyrosine-dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2 domain.

The SHC proteins have been implicated in insulin receptor (IR) signaling. In this study, we used the sensitive two-hybrid assay of protein-protein interaction to demonstrate that SHC interacts directly with the IR. The interaction is mediated by SHC amino acids 1 to 238 and is therefore independent of the Src homology 2 domain. The interaction is dependent upon IR autophosphorylation, since the interaction is eliminated by mutation of the IR ATP-binding site. In addition, mutational analysis of the Asn-Pro-Glu-Tyr (NPEY) motif within the juxtamembrane domain of the IR showed the importance of the Asn, Pro, and Tyr residues to both SHC and IR substrate 1 (IRS-1) binding. We conclude that SHC interacts directly with the IR and that phosphorylation of Tyr-960 within the IR juxtamembrane domain is necessary for efficient interaction. This interaction is highly reminiscent of that of IRS-1 with the IR, and we show that the SHC IR-binding domain can substitute for that of IRS-1 in yeast and COS cells. We identify a homologous region within the IR-binding domains of SHC and IRS-1, which we term the SAIN (SHC and IRS-1 NPXY-binding) domain, which may explain the basis of these interactions. The SAIN domain appears to represent a novel motif which is able to interact with autophosphorylated receptors such as the IR.

Amino Acid Sequence↗

Immunoregulatory effects of the herba Epimediia glycoside icariin.

The in vitro effects of the Chinese Herba Epimediia glycoside icariine (ICA), a chinese herbal extract, on human immune responses were investigated. ICA induced a weak and delayed proliferation of peripheral blood mononuclear cells from healthy donors when compared to phytohemagglutinin. Both T- (TCR alpha beta+) and B cells were the ICA-responding cells. Within T-cells, the relative proportion of CD4-8+ cells increased but that of CD4+8- cells decreased. ICA in certain concentrations could increase lymphokine-activated killer cell (LAK) activity (0.1 to 1.0 microgram/ml) in both tumor patients and healthy donors, and natural killer cell (NK) activity (1.0 to 5.0 micrograms/ml) in tumor patients. Moreover, ICA stimulated the production of tumor necrosis factor-alpha in monocytes from healthy donors. These findings provide evidence that ICA could be applied to adoptive immunotherapy. Generation of LAK cells in presence of an appropriate dose of ICA might be superior to interleukin-2 alone.

Adjuvants, Immunologic↗

[Investigation of the relationship between white lesion of vulva and human epidermal growth factor].

The levels of human epidermal growth factor (hEGF) were determined by radioimmunoassay (RIA) in dermal specimens taken from lesion skin and normal vulva skin in 30 patients with white lesions of the vulva as well as their urine specimens, and in another 29 vulva biopsy and 37 urine samples from healthy women without the disease as the control group. The results showed that the mean hEGF levels in lesion vulva skin, normal vulva skin of the patients and normal vulva skin of healthy women were 163.40 +/- 97.89 micrograms/L, 119.00 +/- 53.13 micrograms/L and 67.84 +/- 14.72 micrograms/L respectively. The level of hEGF in lesion skin was higher than that in the normal vulva skin of same patients (P < 0.05) and also higher than that in the normal skin of healthy women (P < 0.01). The hEGF level in normal skin of the patients was higher than that in healthy women (P < 0.01). The hEGF level in lesion skin had no relationship with pathological types. The hEGF levels in urine had no significant difference between the patients and healthy women. The results suggested that high levels of hEGF in local vulva lesions may play an important role in the pathogenesis of white lesions of the vulva.

Adult↗

[A research on serum, urine and tumor tissue hyaluronate assays for detecting malignant ovarian tumors].

Hyaluronate contents were determined by radioimmunoassay in 91 samples of serum, 88 samples of urine and 32 samples of ovarian tumor tissue from patients with benign and malignant tumors and from healthy subjects. The mean serum hyaluronate level in patients with malignant ovarian tumors (mean, 155.99 micrograms/L, range, 20 to 680 micrograms/L) was significantly higher than that in patients with benign ovarian tumors (mean, 84.2 micrograms/L; range, 20 to 188 micrograms/L) and that in healthy subjects (mean, 57 micrograms/L; range, 2 to 110 micrograms/L). The mean urine hyaluronate level in the malignant group (mean, 307.83 micrograms/L; range 50 to 750 micrograms/L) also was significantly higher than that in the normal control group (mean, 146 micrograms/L; range, 40 to 242 micrograms/L). The results suggest that serum and urine hyaluronate determination in the detection of malignant ovarian tumors is of clinical value.

Adult↗

[Conservative surgery and radiotherapy for early breast cancer].

Thirty-six patients with early stage breast cancer were treated by quadrantectomy, axillary dissection and radiotherapy (CSRT) between October 1987 and May 1990. The median follow-up was 48 months. Overall survival was 100%. 2 had local recurrence in the breast, both patients were stage IIB (T2N1), the number of positive node were 6/12 and 3/11, respectively. The cosmetic results of the breast are excellent and good in 91%. We concluded that CSRT provides good cosmetic results and better local tumor control for early breast cancer patients, but good results depend on strict adherence to indication of treatment, fair surgical techniques and radiotherapeutic measures.

Adult↗

[Full-load expansion techniques and preliminary clinical application].

For accelerating the inflation process of soft tissue expansion, a continuous inflation protocol regarding pain as the criterion of over-inflation, the full-load expansion technique, was introduced. It is carried out by restricting persistently the pressure in the expander near the pain threshold in a state of dynamic equilibrium between the infusing rate and the skin expansion velocity, with a simple and practical assembled device. This inflation is neither at a uniform infusing rate nor at a constant filing pressure. 19 expanders in 13 patients were inflated following this protocol. Their inflations were respectively fulfilled in 5 to 20 days, depending individually on their anatomic regions, total volumes of infusion, areas of the overlying skin and the patient susceptibilities.

Alopecia↗

High proliferative rates demonstrated by bromodeoxyuridine labeling index in breast carcinomas with p53 overexpression.

The protein p53 is a product of a suppressor oncogene. Mutations occurring in 13-15% of breast carcinomas are associated with p53 stainability within nuclei and progression of the tumor. We determined the extent to which p53 abnormality was associated with proliferation by measuring p53 immunohistochemically with a polyclonal antibody and monoclonal PAb1801 in invasive carcinomas of known S-phase fraction (SPF) assessed histologically by bromodeoxyuridine incorporation. Results with the two antibodies always agreed. One of 20 low, 2/18 midrange, and 9/17 high SPF carcinomas were positive for p53. P53 positivity was also related to other indicators of aggressiveness including size of primary tumor, nuclear and nucleolar size, and estrogen and progesterone receptor content, but relationships between p53 and vascular invasion and lymph node metastasis were not found. We conclude that nuclear p53 accumulation is more closely related to proliferation than to invasion and metastasis, and that it identifies some but not all breast carcinomas with high proliferative indices.

Breast Neoplasms↗

Prenatal diagnosis of Sanfilippo disease type C using a simple fluorometric enzyme assay.

A new fluorogenic substrate, 4-methylumbelliferyl beta-D-glucosaminide, was used for the assay of acetyl CoA:glucosaminide N-acetyltransferase in chorionic villi, cultured villus cells, and amniocytes. Optimal conditions for the assay and the ranges of enzyme activity were established for the various types of fetal cells. This simple fluorometric assay provides a reliable method for early prenatal diagnosis of Sanfilippo disease type C which is more convenient than current methods using radiolabelled substrates. The method was applied to amniotic fluid cells and fetal fibroblasts from an at-risk pregnancy in which an affected fetus was diagnosed by two-dimensional electrophoresis of glycosaminoglycans in the amniotic fluid.

Acetylglucosamine↗

Accelerated G1-transit following transient inhibition of DNA replication is dependent on two processes.

Accelerated G1 transit in HeLa cells develops after a temporary inhibition of DNA synthesis in the previous generation. G1 acceleration has been found to be dependent on (1) the cell-cycle position at the time of the inhibition and (2) the duration of the inhibition. The degree of G1 acceleration correlates with the position in S-phase at which DNA synthesis is blocked. G1 transit time decreases gradually beginning with early S blocks and reaches a minimum when DNA synthesis is inhibited at mid S-phase. A minimum of 4 h continuous inhibition at this position resulted in maximum G1 acceleration. Unbalanced growth, i.e., the nonspecific increase in total protein or RNA levels that results from inhibition of DNA synthesis, did not correlate with the decrease in G1 transit time. On the other hand, one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed specific changes in four nuclear proteins of molecular weights 120, 66, 57, and 51 kDa in cells immediately following release from inhibition of DNA synthesis at mid S-phase. A Western blot analysis of cyclins D and E showed an increased accumulation of cyclin E at 0, 1, 5, 7, and 12 h following cell release from the mid S-phase block. Therefore, it is unlikely that changes in the ratio of protein/DNA or RNA/DNA are responsible for the decrease in G1 transit times as suggested by the unbalanced growth model of G1 acceleration. Instead, G1 acceleration may result from the accumulation during S-phase blockage, and subsequent retention through G2 and mitosis, of specific proteins required for cell transit through G1 in the next cell cycle.

Aphidicolin↗