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J Gao

Publications and source records attributed to J Gao.

At least 271 records · Page 15Linked to original sources
PubMed1998

A unified theory of the role of the ocular surface in dry eye.

It is our belief that the pathology of dry eye occurs when systemic androgen levels fall below the threshold necessary for support of secretory function and generation of an anti-inflammatory environment (Fig. 3). When this occurs, both the lacrimal gland and the ocular surface become irritated and inflamed, and they secrete cytokines that interfere with the normal neural connections that drive the tearing reflex. This leaves the lacrimal gland in an isolated condition, perhaps exacerbating atrophic alterations of the glandular tissue. These changes allow for antigen presentation at the surface of the lacrimal acinar cells and increase lymphocytic infiltration of the gland. A similar series of events may be occurring on the ocular surface. From this hypothesis we conclude: 1. The ocular surface, lacrimal gland, and interconnecting innervation act as an integrated servo-mechanism. 2. Once the lacrimal gland loses its androgen support, it is subject to immune/neurally mediated dysfunction. 3. The ocular surface is an appropriate target for dry eye therapeutics.

Animals↗
PubMed1998

The inhibitory effect of beta-stimulation on the Na/K pump current in guinea pig ventricular myocytes is mediated by a cAMP-dependent PKA pathway.

The beta-agonist isoproterenol (ISO) reduces the Na/K pump current (Ip) via beta-adrenergic receptors when the intracellular calcium concentration ([Ca2+]i) is below 150 nM [8]. In the present study, the intracellular signaling pathway was investigated with whole-cell patch-clamp of isolated guinea pig ventricular myocytes. The inhibitory effect of ISO could be mimicked by external application of the membrane-permeant cAMP analog chlorophenylthio-cAMP (0.5 mM), the phosphodiesterase inhibitor isobutyl-1-methylxanthine (IBMX, 100 microM), or the adenylyl cyclase activator forskolin (50 microM). Intracellular application of the synthetic peptide inhibitor of protein kinase A (PKA), PKI (5 microM), prevented the effect of ISO. These results suggest that the inhibitory effect of ISO on Ip is mediated via a phosphorylation step induced by a cAMP-dependent PKA pathway. Neither the non-specific protein kinase inhibitor H7 (100 microM) nor the protein phosphatase inhibitor calyculin A (0.5 microM) had any effect on Ip in the absence of ISO. However, H7 could increase Ip and calyculin A could reduce it in the presence of ISO (1 microM and 12 nM respectively). These results indicate that there is a low basal level of phosphorylation which makes the effects of H7 and calyculin A difficult to detect in the absence of an ISO-induced increase in phosphorylation level.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

Loss of conformational stability in calmodulin upon methionine oxidation.

We have used electrospray ionization mass spectrometry (ESI-MS), circular dichroism (CD), and fluorescence spectroscopy to investigate the secondary and tertiary structural consequences that result from oxidative modification of methionine residues in wheat germ calmodulin (CaM), and prevent activation of the plasma membrane Ca-ATPase. Using ESI-MS, we have measured rates of modification and molecular mass distributions of oxidatively modified CaM species (CaMox) resulting from exposure to H2O2. From these rates, we find that oxidative modification of methionine to the corresponding methionine sulfoxide does not predispose CaM to further oxidative modification. These results indicate that methionine oxidation results in no large-scale alterations in the tertiary structure of CaMox, because the rates of oxidative modification of individual methionines are directly related to their solvent exposure. Likewise, CD measurements indicate that methionine oxidation results in little change in the apparent alpha-helical content at 28 degrees C, and only a small (0.3 +/- 0.1 kcal mol(-1)) decrease in thermal stability, suggesting the disruption of a limited number of specific noncovalent interactions. Fluorescence lifetime, anisotropy, and quenching measurements of N-(1-pyrenyl)-maleimide (PMal) covalently bound to Cys26 indicate local structural changes around PMal in the amino-terminal domain in response to oxidative modification of methionine residues in the carboxyl-terminal domain. Because the opposing globular domains remain spatially distant in both native and oxidatively modified CaM, the oxidative modification of methionines in the carboxyl-terminal domain are suggested to modify the conformation of the amino-terminal domain through alterations in the structural features involving the interdomain central helix. The structural basis for the linkage between oxidative modification and these global conformational changes is discussed in terms of possible alterations in specific noncovalent interactions that have previously been suggested to stabilize the central helix in CaM.

Amino Acid Sequence↗
PubMed1998

The comparative trial of TCu 380A IUD and progesterone-releasing vaginal ring used by lactating women.

The objective of this paper was to compare the efficacy, acceptability, safety, and bleeding pattern of TCu 380A intrauterine device (IUD) and progesterone-releasing vaginal ring used by breastfeeding women. The study population included 97 breastfeeding women using IUD and 100 women using vaginal ring. Of the IUD users, no insertion failure, perforation, or accidental pregnancy occurred in 12 months. There was one IUD expulsion. There were no discontinuations of IUD due to medical reasons other than expulsion. The total discontinuation rate was 2.3%. In the ring group, no accidental pregnancy occurred. The major reasons for discontinuation were ring use-related problems and vaginal problems. The total discontinuation rate was 65.4% within 1 year. The frequency of any one complaint among the ring users was higher than that among the IUD users. There were no differences in the proportion of women having no sexual activity and in the weight of their babies between the two groups. Compared with the IUD users, the median number of bleeding/spotting (B/S) episodes and B/S days of the vaginal ring users were fewer; consequently, the mean length of B/S-free interval was longer in all four reference periods; the mean length of B/S episode and segment were the same; the occurrence of amenorrhea was more frequent; in contrast, the proportions of normal bleeding patterns were fewer. The frequencies of prolonged bleeding, frequent bleeding, and infrequent bleeding patterns did not differ between the two groups. The percentage of irregular bleeding was fewer only in the first two reference periods. It is concluded that the TCu 380A IUD and progesterone-releasing vaginal ring used by breastfeeding women are safe and effective. The higher discontinuation rate of the ring users was mainly because of use-related problems. Breastfeeding women with TCu 380A IUD had better tolerance and acceptability. The TCu 380A IUD does not, but the progesterone-releasing vaginal ring does, suppress the recovery of ovarian function. However, once return of menstruation occurred, there were no differences in bleeding patterns between the two contraceptive methods.

Administration, Intravaginal↗
PubMed1998

Multidisciplinary weight management in locoregional breast cancer: results of a phase II study.

Sixty-one women with newly diagnosed locoregional breast cancer (T1-3, N0-1, M0) having an initial Body Mass Index (BMI) between 20 and 35 kg/m2 who were receiving standard adjuvant treatment (chemotherapy, tamoxifen, and/or radiation) were asked to avoid weight gain (if initial BMI < or = 25 kg/m2) or to lose up to 10 kg (if initial BMI 25-35 kg/m2) over one year. Women participated in twenty group sessions (10 weekly, 10 monthly) which involved a psychological supportive-expressive group intervention supplemented by individual weight goals, and nutrition and exercise programs. Fifty-five non-censored women (5 developed recurrence, 1 died of a subarachnoid hemorrhage) lost a mean of 0.53 +/- 3.72 kg. Weight loss was greatest in initially overweight women (BMI > or = 25 kg/m2) who lost 1.63 +/- 4.11 kg (p = 0.01 compared to normal weight women) and in those not receiving chemotherapy who lost 2.15 +/- 2.83 kg (p = 0.0004 compared to those receiving chemotherapy). 70.9% met predefined criteria for success. Aerobic exercise increased significantly during the intervention (p = 0.00005) and was the strongest predictor of success (OR 1.73 for each additional 30 minutes of exercise weekly, p = 0.003). Changes in caloric intake were not significant, but fat intake decreased and carbohydrate and fibre intake increased significantly during the intervention. Eating behavior and psychological status improved significantly. Thus, this multidisciplinary weight management intervention successfully prevented weight gain in women with newly diagnosed locoregional breast cancer, and helped overweight women lose weight.

Adult↗
PubMed1998

The menisci of the knee joint. Anatomical and functional characteristics, and a rationale for clinical treatment.

The menisci and their insertions into bone (entheses) represent a functional unit. Thanks to their firm entheses, the menisci are able to distribute loads and therefore reduce the stresses on the tibia, a function which is regarded essential for cartilage protection and prevention of osteoarthrosis. The tissue of the hypocellular meniscal body consists mainly of water and a dense elaborate type I collagen network with a predominantly circumferential alignment. The content of different collagens, proteoglycans and nonproteoglycan proteins shows significant regional variations probably reflecting functional adaptation. The meniscal horns are attached via meniscal insertional ligaments mainly to tibial bone. At the enthesis, the fibres of the insertional ligaments attach to bone via uncalcified and calcified fibrocartilages. This anatomical configuration of gradual transition from soft to hard tissue, which is identical to other ligament entheses, is certainly essential for normal mechanical function and probably protects this vulnerable transition between 2 biomechanically different tissues from failure. Clinical treatment of meniscal tears needs to be based on these special anatomical and functional characteristics. Partial meniscectomy will preserve some of the load distribution function of the meniscus only when the meniscal body enthesis entity is preserved. Repair of peripheral longitudinal tears will heal and probably preserve the load distribution function of the meniscus, whereas radial tears through the whole meniscal periphery or more central and complex tears may be induced to heal, but probably do not preserve the load distribution function. There is no proof that replacement of the meniscus with an allograft can reestablish some of the important meniscal functions, and thereby prevent or reduce the development of osteoarthrosis which is common after meniscectomy. After implantation, major problems are the remodelling of the graft to inferior structural, biochemical and mechanical properties and its insufficient fixation to bone which fails to duplicate a normal anatomical configuration and therefore a functional meniscal enthesis.

Animals↗
PubMed1998

Regional differences in cell shape and gap junction expression in rat Achilles tendon: relation to fibrocartilage differentiation.

Tendon cells have complex shapes, with many cell processes and an intimate association with collagen fibre bundles in their extracellular matrix. Where cells and their processes contact one another, they form gap junctions. In the present study, we have examined the distribution of gap junction components in phenotypically different regions of rat Achilles tendon. This tendon contains a prominent enthesial fibrocartilage at its calcaneal attachment and a sesamoid fibrocartilage where it is pressed against the calcaneus just proximal to the attachment. Studies using DiI staining demonstrated typical stellate cell shape in transverse sections of pure tendon, with cells withdrawing their cell processes and rounding up in the fibrocartilaginous zones. Coincident with change in shape, cells stopped expressing the gap junction proteins connexins 32 and 43, with connexin 43 disappearing earlier in the transition than connexin 32. Thus, there are major differences in the ability of cells to communicate with one another in the phenotypically distinct regions of tendon. Individual fibrocartilage cells must sense alterations in the extracellular matrix by cell/matrix interactions, but can only coordinate their behaviour via indirect cytokine and growth factor signalling. The tendon cells have additional possibilities--in addition to the above, they have the potential to communicate direct cytoplasmic signals via gap junctions. The formation of fibrocartilage in tendons occurs because of the presence of compressive as well as tensile forces. It may be that different systems are used to sense and respond to such forces in fibrous and cartilaginous tissues.

Achilles Tendon↗
PubMed1998

The pathology of dry eye: the interaction between the ocular surface and lacrimal glands.

BACKGROUND: Most dry-eye symptoms result from an abnormal, nonlubricative ocular surface that increases shear forces under the eyelids and diminishes the ability of the ocular surface to respond to environmental challenges. This ocular-surface dysfunction may result from immunocompromise due to systemic autoimmune disease or may occur locally from a decrease in systemic androgen support to the lacrimal gland as seen in aging, most frequently in the menopausal female. HYPOTHESIS: Components of the ocular surface (cornea, conjunctiva, accessory lacrimal glands, and meibomian glands), the main lacrimal gland, and interconnecting innervation act as a functional unit. When one portion is compromised, normal lacrimal support of the ocular surface is impaired. Resulting immune-based inflammation can lead to lacrimal gland and neural dysfunction. This progression yields the OS symptoms associated with dry eye. THERAPY: Restoration of lacrimal function involves resolution of lymphocytic activation and inflammation. This has been demonstrated in the MRL/lpr mouse using systemic androgens or cyclosporine and in the dry-eye dog using topical cyclosporine. The efficacy of cyclosporine may be due to its immunomodulatory and antiinflammatory (phosphatase inhibitory capability) functions on the ocular surface, resulting in a normalization of nerve traffic. CONCLUSION: Although the etiologies of dry eye are varied, common to all ocular-surface disease is an underlying cytokine/receptor-mediated inflammatory process. By treating this process, it may be possible to normalize the ocular surface/lacrimal neural reflex and facilitate ocular surface healing.

Animals↗
PubMed1998

The role of apoptosis in the pathogenesis of canine keratoconjunctivitis sicca: the effect of topical Cyclosporin A therapy.

PURPOSE: The exact etiology of dry eye is unknown but is believed to be multifactorial. Apoptosis has been implicated in the pathogenesis of autoimmune diseases such as Sjögren's syndrome (SS). This study attempted to gain a better understanding of the role of apoptosis and its regulation in the patho-physiology of dry eye. The therapeutic effect of immunomodulatory agents such as cyclosporin A (CsA) in the treatment of dry eye, particularly its impact on the level of apoptosis in the target tissues, is also investigated. METHODS: A colony of dogs with spontaneous chronic idiopathic keratoconjunctivitis sicca (KCS) was maintained. Nictitans lacrimal gland (NLG), an accessory lacrimal gland, and conjunctival biopsies of the KCS and normal dogs were obtained before and after 12 weeks of treatment with 0.2% topical CsA ophthalmic emulsion b.i.d. (Allergan, Inc., Irvine, CA, U.S.A.). Tissues were prepared for the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) apoptosis assay and immunohistochemical analysis for various apoptosis mediators. RESULTS: The TUNEL assay demonstrated that (i) the normal NLG and conjunctival epithelial cells exhibited a limited level of apoptosis; (ii) in KCS dogs, lacrimal acinar and conjunctival epithelial cells underwent an increased apoptosis, whereas the lymphocytes had a significantly lower level of apoptosis compared to those of the normal dogs; (iii) after topical CsA, apoptosis was induced in the lymphocytes and suppressed in the acinar and conjunctival epithelial cells in KCS dogs. Immunohistochemistry revealed that p53, fas, and fasL, but not bcl-2 were highly expressed in the target tissues of KCS dogs. The immunoreactivity of p53 was significantly decreased, whereas the bcl-2 level was increased after CsA administration. CONCLUSIONS: The induction of epithelial cell apoptosis and the suppression of lymphocytic apoptosis in the NLG and ocular-surface tissues, such as conjunctiva of KCS dogs, indicates the important role of this phenomenon in the etiology of dry eye. Topical CsA appears to facilitate lymphocytic apoptosis and suppress epithelial cell apoptosis in the KCS dog. The differential expression of various apoptotic mediators after topical treatment implicates CsA in facilitating the reestablishment of the normal apoptotic balance, suggesting additional mechanisms by which CsA is therapeutic for dry-eye syndrome.

Administration, Topical↗
PubMed1998

No requirement for V(D)J recombination in p53-deficient thymic lymphoma.

The p53 tumor suppressor is activated in response to a variety of cellular stress signals, although specific in vivo signals that trigger tumor suppression are unknown. In mouse thymocytes, where p53 inactivation leads to tumorigenesis, several observations suggest that V(D)J recombination of T-cell receptor (TCR) loci could provide a DNA damage signal triggering p53-dependent apoptosis and tumor suppression. Inactivation of p53 would allow V(D)J driven mutation of additional cancer genes, facilitating tumorigenesis. Here, we show that mice with a p53 deficiency in thymocytes and unable to carry out V(D)J recombination are not impaired in the development of thymoma. Recombination-activating gene (RAG) deficiencies were introduced into both p53-/- mice and TgTDeltaN transgenic mice, a strain in which 100% of the mice develop thymoma due to thymocyte-specific inactivation of p53 by a simian virus 40 T-antigen variant. V(D)J recombination was dispensable for tumorigenesis since thymomas developed with or without the RAG-1 or RAG-2 gene, although some delay was observed. When V(D)J recombination was suppressed by expression of rearranged TCR transgenes, 100% of the TgTDeltaN mice developed thymoma, surprisingly with reduced latency. Further introduction of a RAG deficiency into these mice had no impact on the timing or frequency of tumorigenesis. Finally, karyotype and chromosome painting analyses showed no evidence for TCR gene translocations in p53-deficient thymomas, although abundant aneuploidy involving frequent duplication of certain chromosomes was present. Thus, contrary to the current hypothesis, these studies indicate that signals other than V(D)J recombination promote p53 tumor suppression in thymocytes and that the mechanism of tumorigenesis is distinct from TCR translocation oncogene activation.

Animals↗
PubMed1998

Lactate clamp: a method to measure lactate utilization in vivo.

A lactate clamp method has been developed to quantify the whole body lactate utilization in conscious, unstressed rats. Dichloroacetate (DCA), a known lactate utilization enhancer, was used to validate the method. Fasting blood lactate concentrations before the clamps were identical for DCA-treated (1 mmol/kg) and control groups (1.65 +/- 0.37 vs. 1.65 +/- 0.19 mM). The animals received a primed continuous lactate infusion for 90 min at variable rates to clamp the blood lactate concentration at 2 mM. The steady-state (60-90 min) lactate infusion rate, which represents the whole body lactate utilization in DCA-treated animals, was 144% higher than that in the control animals (13.2 +/- 1.0 vs. 5.4 +/- 1.1 mg . kg-1 . min-1; P < 0.001). The markedly increased lactate infusion rate indicates an enhanced lactate flux by DCA. To determine whether the increased lactate infusion by DCA reflected reduced endogenous lactate production, lactate production was measured. The results indicate that endogenous lactate production was not affected by DCA. In conclusion, the lactate clamp provides a sensitive and reliable method to assess lactate utilization in vivo, a dynamic measurement that may not be clearly demonstrated by blood lactate concentrations per se.

Animals↗
PubMed1998

Expression of transforming growth factor-beta 1 (TGF-beta1) in the developing periodontium of rats.

Transforming growth factor-beta 1 (TGF-beta1) has been reported to be expressed within several tissue compartments of developing molar crowns and therefore is implicated in tooth development. Additionally, TGF-beta1 may also play a crucial role in tissue repair and regeneration. The aim of this study was to determine the distribution of TGF-beta1 in the developing periodontal attachment apparatus (cementum, periodontal ligament, and alveolar bone) in Lewis rats. Animals aged 3, 6, and 12 wks were killed, their mandibles removed, fixed, demineralized, and processed in paraffin. The localization of TGF-beta1 in tissues was detected by polyclonal goat antibodies against human TGF-beta1 by means of immunoperoxidase techniques. TGF-beta1 messenger RNA was detected by in situ hybridization with a cocktail oligonucleotide probe. Cell counts were determined for analysis of the percentage of cells stained positive for TGF-beta1. Results revealed that TGF-beta1 was expressed in the developing alveolar bone, periodontal ligament, and cementum at all stages of tissue development studied. Staining was stronger at sites of cementum and alveolar bone compared with the periodontal ligament. Intensity of the positive staining, based on 3 grades, indicated a similarity between the tissues obtained from different ages, but varied between several cell types. Cementoblasts and osteoblasts stained more strongly than fibroblasts. Large numbers (approximately 90%) of the osteocytes in developing bone expressed TGF-beta1; however, in mature bone, fewer osteocytes stained for TGF-beta1. The percentages of positively stained cementoblasts, osteoblasts, and fibroblasts in the periodontal space were greater at the apical portion than at the cervical portion of the root. TGF-beta1 mRNA was expressed in osteoblasts, some bone marrow cells, cementoblasts, and fibroblasts. This study indicates that TGF-beta1 may play an important role in the modulation of tissue formation and development of the periodontium.

Aging↗
PubMed1998

Influence of recombinant retroviral vector expressing antisense TGF alpha on malignant phenotype of human pancreatic carcinoma cell line.

OBJECTIVE: To observe the effects of antisense TGF alpha on the growth of human pancreatic carcinoma cell line cells. METHODS: A recombinant retroviral vector expressing antisense TGF alpha was constructed, and transfected the ecotropic packaging cell line psi-2 with lipofectin. After the amphotropic packaging cell line PA317 was transfected with the virus supernatant of psi-2, the replication-defective, amphotropic retroviral supernatant was used to infect human pancreatic carcinoma cell line PC-7. Following puromycin selection, puromycin-resistant colonies were pooled and expanded to a cell line PC-7/AS-TGF alpha. RESULTS: The retroviral integration in the genomes of psi-2, PA317 and transformant PC-7 cells was confirmed by Southern blot hybridization. Northern blot hybridization showed a down regulation of endogenous TGF alpha in PC-7/AS-TGF alpha cell line. The high levels of growth inhibition and reduction of 3H-TdR incorporation in PC-7/AS-TGF alpha were evident. Also, the soft agar colony-formation and tumorigenicity in nude mice were significantly suppressed by antisense TGF alpha. CONCLUSION: The antisense TGF alpha expressing vector can block the target gene expression, suppress the cell growth and partially reverse the malignant phenotype of pancreatic carcinoma cells.

3T3 Cells↗
PubMed1998

Enhancing effects of beta-endorphin on glutamate neurotoxicity.

AIM: To study the effect of beta-endorphin (beta-End) on monosodium glutamate (MSG)-induced neurotoxicity (GNT). METHODS: Image analysis of neuronal areas and determination of mitochondrial membrane protein-bound Ca2+ and intracellular free Ca2+ ([Ca2+]i) were used. RESULTS: beta-End aggravated MSG-induced neuronal injury in arcuate nucleus of hypothalamus in a dose-dependent manner in the range from 0.5 to 5.0 mg.kg-1. MSG-induced increase in mitochondrial membrane protein-bound Ca2+ was enhanced when treated with beta-End 2 g.L-1. MSG-induced elevation in [Ca2+]i in single neuron was also augmented from 320 +/- 84 to 589 +/- 78 nmol.L-1 by the treatment with beta-End 2 g.L-1. CONCLUSION: beta-End enhanced GNT via aggravating the disruption of intracellular Ca2+ homeostasis induced by MSG.

Animals↗
PubMed1998

[The dynamic changes and significances of endothelins in early burned rats].

OBJECTIVE: To elucidate the significance of endothelins in visceral injury at the early stage of burn. METHODS: By use of a 30% (III degree) total body surface area (TBSA) burn rat model, we measured the concentration of endothelins in plasma, heart, liver, lung, kidney, and observed the effects of PD145065, a kind of non-selective ETA-ETB receptor antagonist, on visceral impairment. RESULTS: Not only did the endothelin concentration in plasma of burnt rat elevated significantly, showing a peak at 6 hours postburn, but also the endothelin contents in internal organs apparently increased. The changes in endothelin in liver or kidney were negatively correlated with the alteration in renal or hepatic blood flow. Moreover, administration of endothelin receptor antagonist PD145065, without affecting the arterial blood pressure, could revert the decrease of renal or hepatic blood flow to some extent, reduce the water contents of heart, liver, lung, kidney postburn. CONCLUSION: The abnormal changes in endothelins postburn contribute to visceral injury in the early postburn stage in rats.

Animals↗
PubMed1998

A kinetics study on the production of alkaline proteinase by Bacillus licheniformis 2709.

With automatic control fermentation equipment, the kinetics of growth and metabolism of Bacillus licheniformis 2709 was studied with batch culture as well as with fed-batch-culture by controlling the concentration of the growth-limiting substrate. The Monod formula proved to be reasonable in describing the relationship between cell growth rate of B. licheniformis 2709 and the concentration of the growth-limiting substrate in the broth, and the data of product synthesis rate showed that the fermentation type belongs to one partially related to growth.

Bacillus↗