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Biomedical subjects

H Cheng

Publications and source records attributed to H Cheng.

At least 163 records · Page 9Linked to original sources
PubMed1999

The National Diabetic Retinopathy Laser Treatment Audit. III. Clinical outcomes.

PURPOSE: To describe the short-term clinical outcomes for a cohort of patients undergoing first photocoagulation treatment for proliferative retinopathy or maculopathy in the United Kingdom. METHOD: Nine-month follow-up of the Royal College of Ophthalmologists' national audit of laser treatment for diabetic retinopathy. RESULTS: For eyes with maculopathy, 9.2% had had a deterioration in visual acuity equivalent to a doubling of the visual angle and 3.3% of eyes had a visual acuity of less than 6/60 at follow-up. There had been an improvement in the macular oedema or exudate in 64.6% and 77.3% respectively. Prognostic factors for a poorer visual acuity at follow-up were worse visual acuity at baseline, the presence of diffuse (vs focal) oedema and grid (vs focal) treatment. For eyes with proliferative retinopathy, the retinal neovascularisation had regressed fully in 50.8% of cases, whilst there had been no change or a deterioration in 10.3%. A visual acuity of less than 6/60 at follow-up was present in 8.6% of eyes. There was a poor morphological outcome at follow-up (as defined by rubeosis, new tractional detachment or having had a vitrectomy) in 7.2%. Risk factors for poor morphological outcome were the presence of 'high-risk characteristics', female sex and the presence of concurrent maculopathy at baseline. Regression of neovascularisation was associated with greater areas of retinal ablation at the initial treatment session. Although some eyes with proliferative retinopathy appeared to be undertreated initially compared with DRS and ETDRS protocols, some of these eyes did respond to lower amounts of treatment. CONCLUSION: For maculopathy, poorer outcome was related to worse visual acuity at baseline, diffuse (vs focal) maculopathy, and grid treatment. For proliferative retinopathy, poorer outcome was related to 'high-risk characteristics' and coexistence of maculopathy at baseline, and improvement was related to larger areas of ablation. The relationship of poor outcome with worse initial disease argues for earlier detection of retinopathy.

Diabetic Retinopathy↗
PubMed1999

Local control models of cardiac excitation-contraction coupling. A possible role for allosteric interactions between ryanodine receptors.

In cardiac muscle, release of activator calcium from the sarcoplasmic reticulum occurs by calcium- induced calcium release through ryanodine receptors (RyRs), which are clustered in a dense, regular, two-dimensional lattice array at the diad junction. We simulated numerically the stochastic dynamics of RyRs and L-type sarcolemmal calcium channels interacting via calcium nano-domains in the junctional cleft. Four putative RyR gating schemes based on single-channel measurements in lipid bilayers all failed to give stable excitation-contraction coupling, due either to insufficiently strong inactivation to terminate locally regenerative calcium-induced calcium release or insufficient cooperativity to discriminate against RyR activation by background calcium. If the ryanodine receptor was represented, instead, by a phenomenological four-state gating scheme, with channel opening resulting from simultaneous binding of two Ca2+ ions, and either calcium-dependent or activation-linked inactivation, the simulations gave a good semiquantitative accounting for the macroscopic features of excitation-contraction coupling. It was possible to restore stability to a model based on a bilayer-derived gating scheme, by introducing allosteric interactions between nearest-neighbor RyRs so as to stabilize the inactivated state and produce cooperativity among calcium binding sites on different RyRs. Such allosteric coupling between RyRs may be a function of the foot process and lattice array, explaining their conservation during evolution.

Algorithms↗
PubMed1999

Mismatch repair gene defects contribute to the genetic basis of double primary cancers of the colorectum and endometrium.

Hereditary non-polyposis colorectal cancer (HNPCC) is a dominantly inherited cancer syndrome caused by germline defects of mismatch repair (MMR) genes. Endometrial cancer is the most common extracolonic neoplasm in HNPCC and is the primary clinical manifestation of the syndrome in some families. The cumulative incidence of endometrial cancer among HNPCC mutation carriers is high, estimated to be from 22 to 43%. We hypothesized that women with double primary cancers of the colorectum and endometrium are likely to be members of HNPCC families. In order to determine how frequently HNPCC manifests in the context of double primary cancers, we examined alterations of two MMR genes, hMSH2 and hMLH1, in 40 unrelated women affected with double primary cancers. These cases were identified using hospital-based and population-based cancer registries in Ontario, Canada. MMR gene mutations were screened by single-strand conformation polymorphism analysis and confirmed by direct sequencing. Eighteen percent (seven of 40) were found to harbor mutations of one of the two MMR genes. Analysis of colorectal and/or endometrial tumors of mutation-negative probands found microsatellite instability in seven of 20 cases. Six of seven mutation-positive probands had strong family histories suggestive of HNPCC. First degree relatives of mutation-positive probands had a very high relative risk (RR) of colorectal cancer (RR = 8.1, CI 3. 5-15.9) and endometrial cancer (RR = 23.8, CI 6.4-61.0). The relative risk of mutation-negative cases was 2.8 (CI 1.7-4.5) for colorectal cancer and 5.4 (CI 2.0-11.7) for endometrial cancer. We recommend that all double primary patients with cancers at these sites should have a genetic evaluation, including molecular analysis for HNPCC where appropriate.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Spontaneous beta(2)-adrenergic signaling fails to modulate L-type Ca(2+) current in mouse ventricular myocytes.

A receptor can be activated either by specific ligand-directed changes in conformation or by intrinsic, spontaneous conformational change. In the beta(2)-adrenergic receptor (AR) overexpression transgenic (TG4) murine heart, spontaneously activated beta(2)AR (beta(2)-R*) in the absence of ligands has been evidenced by elevated basal adenylyl cyclase activity and cardiac function. In the present study, we determined whether the signaling mediated by beta(2)-R* differs from that of a ligand-elicited beta(2)AR activation (beta(2)-LR*). In ventricular myocytes from TG4 mice, the properties of L-type Ca(2+) current (I(Ca)), a major effector of beta(2)-LR* signaling, was unaltered, despite a 2.5-fold increase in the basal cAMP level and a 1.9-fold increase in baseline contraction amplitude as compared with that of wild-type (WT) cells. Although the contractile response to beta(2)-R* in TG4 cells was abolished by a beta(2)AR inverse agonist, ICI118,551 (5 x 10(-7) M), or an inhibitory cAMP analog, Rp-CPT-cAMPS (10(-4) M), no change was detected in the simultaneously recorded I(Ca). These results suggest that the increase in basal cAMP due to beta(2)-R*, while increasing contraction amplitude, does not affect I(Ca) characteristics. In contrast, the beta(2)AR agonist, zinterol elicited a substantial augmentation of I(Ca) in both TG4 and WT cells (pertussis toxin-treated), indicating that L-type Ca(2+) channel in these cells can respond to ligand-directed signaling. Furthermore, forskolin, an adenylyl cyclase activator, elicited similar dose-dependent increase in I(Ca) amplitude in WT and TG4 cells, suggesting that the sensitivity of L-type Ca(2+) channel to cAMP-dependent modulation remains intact in TG4 cells. Thus, we conclude that beta(2)-R* bypasses I(Ca) to modulate contraction, and that beta(2)-LR* and beta(2)-R* exhibit different intracellular signaling and target protein specificity.

Adenylate Cyclase Toxin↗
PubMed1999

Regulation of c-Fes tyrosine kinase and biological activities by N-terminal coiled-coil oligomerization domains.

The cytoplasmic protein-tyrosine kinase Fes has been implicated in cytokine signal transduction, hematopoiesis, and embryonic development. Previous work from our laboratory has shown that active Fes exists as a large oligomeric complex in vitro. However, when Fes is expressed in mammalian cells, its kinase activity is tightly repressed. The Fes unique N-terminal sequence has two regions with strong homology to coiled-coil-forming domains often found in oligomeric proteins. Here we show that disruption or deletion of the first coiled-coil domain upregulates Fes tyrosine kinase and transforming activities in Rat-2 fibroblasts and enhances Fes differentiation-inducing activity in myeloid leukemia cells. Conversely, expression of a Fes truncation mutant consisting only of the unique N-terminal domain interfered with Rat-2 fibroblast transformation by an activated Fes mutant, suggesting that oligomerization is essential for Fes activation in vivo. Coexpression with the Fes N-terminal region did not affect the transforming activity of v-Src in Rat-2 cells, arguing against a nonspecific suppressive effect. Taken together, these findings suggest a model in which Fes activation may involve coiled-coil-mediated interconversion of monomeric and oligomeric forms of the kinase. Mutation of the first coiled-coil domain may activate Fes by disturbing intramolecular coiled-coil interaction, allowing for oligomerization via the second coiled-coil domain. Deletion of the second coiled-coil domain blocks fibroblast transformation by an activated form of c-Fes, consistent with this model. These results provide the first evidence for regulation of a nonreceptor protein-tyrosine kinase by coiled-coil domains.

Animals↗
PubMed1999

Characterization of receptors mediating AVP- and OT-induced glucagon release from the rat pancreas.

We characterized the receptors that mediate arginine vasopressin (AVP)- and oxytocin (OT)-induced glucagon release by use of a number of antagonists in the perfused rat pancreas and the fluorescence imaging of the receptors. AVP and OT (3 pM-3 nM) increased glucagon release in a concentration-dependent manner. The antagonist with potent V(1b) receptor-blocking activity, CL-4-84 (10 nM), abolished AVP (30 pM)-induced glucagon release but did not alter OT (30 pM)-induced glucagon release. d(CH(2))(5)[Tyr(Me)(2)]AVP (10 nM), a V(1a) receptor antagonist, and L-366,948 (10 nM), a highly specific OT-receptor antagonist, failed to inhibit AVP-induced glucagon release. In contrast, L-366,948 (10 nM) abolished OT (30 pM)-induced glucagon release but did not change the effect of AVP. Fluorescent microscopy of rat pancreatic sections showed that fluorescence-labeled AVP and OT bound to their receptors in the islets of Langerhans and that the bindings were inhibited by 1 microM of Cl-4-84 and L-366,948, respectively. Because AVP and OT at physiological concentrations (3-30 pM) increased glucagon release, we conclude that AVP and OT increase glucagon release under the physiological condition through the activation of V(1b) and OT receptors, respectively.

Animals↗
PubMed1999

Effect of hypertonicity on augmentation and potentiation and on corresponding quantal parameters of transmitter release.

Augmentation and (posttetanic) potentiation are two of the four components comprising the enhanced release of transmitter following repetitive nerve stimulation. To examine the quantal basis of these components under isotonic and hypertonic conditions, we recorded miniature endplate potentials (MEPPs) from isolated frog (Rana pipiens) cutaneous pectoris muscles, before and after repetitive nerve stimulation (40 s at 80 Hz). Continuous recordings were made in low Ca2+ high Mg2+ isotonic Ringer solution, in Ringer that was made hypertonic with 100 mM sucrose, and in wash solution. Estimates were obtained of m (no. of quanta released), n (no. of functional release sites), p (mean probability of release), and vars p (spatial variance in p), using a method that employed MEPP counts. Hypertonicity abolished augmentation without affecting potentiation. There were prolonged poststimulation increases in m, n, and p and a marked but transient increase in vars p in the hypertonic solution. All effects were completely reversed with wash. The time constants of decay for potentiation and for vars p were virtually identical. The results are consistent with the notion that augmentation is caused by Ca2+ influx through voltage-gated calcium channels and that potentiation is due to Na+-induced Ca2+ release from mitochondria. The results also demonstrate the utility of this approach for analyzing the dynamics of quantal transmitter release.

Animals↗
PubMed1999

Determinants of DNA sequence specificity of the androgen, progesterone, and glucocorticoid receptors: evidence for differential steroid receptor response elements.

While androgen, progesterone, and glucocorticoid receptors perform distinct physiological functions by regulating unique sets of genes, in vitro they can transactivate a common high-affinity DNA-binding target. Naturally occurring steroid response elements display nucleotide divergence that lowers binding affinity in comparison to the optimal binding element, but enhances receptor-type specificity. We investigated the role of nucleotide deviations within the DNA-binding site for contribution to steroid receptor specificity. We hypothesized that receptor specificity drives the evolution of binding site sequence, rather than strictly receptor-binding affinity. Receptor-selective targets can evolve by some nucleotides selected on the basis of additional bond energy, and others may be selected by differential tolerance to discourage binding from inappropriate receptors. To identify receptor-specific binding sites, we mimicked these dual selection pressures in a receptor-competitive environment in which DNA binding sites for the androgen or progesterone receptors were selected in the presence of the glucocorticoid receptor. These analyses also demonstrated that steroid receptors strongly select nucleotides in the spacer and flanking regions of the half-site and do so in an asymmetric fashion, indicating that steroid receptors interact with DNA in an allosteric manner that affects the transcriptional activation potential.

Amino Acid Sequence↗
PubMed1999

Selective activation of the probasin androgen-responsive region by steroid hormones.

Glucocorticoid and androgen receptors have been shown to function through the same palindromic glucocorticoid response element (GRE) and yet have differential effects on gene transcription. In this study, we examined the functional and structural relationship of the androgen and glucocorticoid receptors with the androgen responsive region (ARR) of the probasin (PB) gene containing two androgen receptor binding sites, ARBS-1 and ARBS-2. Transfection studies indicated that one copy of each cis-acting DNA element was essential for maximal androgen-induced chloramphenicol acetyltransferase (CAT) activity and that androgen selectivity was maintained when multiple copies of the minimal wild type (wt) androgen responsive region containing both ARBS-1 and ARBS-2 (-244 to -96) were subcloned in front of the thymidine kinase promoter. Furthermore, replacing the androgen response region with 1, 2 or 3 copies of either ARBS-1 or ARBS-2 restored less than 4% of the biological activity seen with the wt PB ARR. Multiple copies of either ARBS-1 or ARBS-2 did not result in glucocorticoid-induced CAT gene activity. By comparison, 1 or 2 copies of the tyrosine aminotransferase (TAT) GRE, as well as the mouse mammary tumour virus GRE, were strong inducers of CAT activity in response to both androgen and glucocorticoid treatment. In addition, band shift assays demonstrated that although the synthetic glucocorticoid receptor, GR-DNA binding domain (GR-DBD), and the synthetic androgen receptor, AR2, could interact with the TAT GRE (dissociation constants Kd of 63.9 and 14.1 respectively), only AR2 but not GR-DBD binding could be detected on ARBS-1 and ARBS-2. Our findings provide further evidence that androgen-induced regulation of gene transcription can occur through androgen-specific DNA binding sites that are distinct from the common GRE.

Androgen-Binding Protein↗
PubMed1999

Identification and immunolocalization of chondroitin sulfate proteoglycans in tooth cementum.

Proteoglycans (PGs) display a great diversity in their core proteins as well as carbohydrate structures and are thought to be involved in many biological functions. Recently we have identified and immunolocalized two keratan sulfate PGs, fibromodulin and lumican, in bovine tooth cementum (Cheng et al., Connect. Tissue Res. 34: 87-96, 1996). The objectives of this study were to identify and characterize chondroitin sulfate (CS) PGs in cementum. In order to explore their potential association with mineral, bovine cementum matrix molecules were fractionated into mineral-unbound and -bound matrices by sequential extraction. Both fractions were subjected to DEAE anion exchange column chromatography and the eluate collected was assayed for C4S and C6S isomers by dot blot immunoassay with specific monoclonal antibodies, 2-B-6 and 3-B-3, respectively. Two families of CSPGs were identified mainly in the mineral-unbound fraction. One contained only C4S glycosaminoglycan and the other both C6S and C4S. By biochemical and immunochemical analyses, decorin and biglycan were identified in the former and versican in the latter. The ratio of C6S to C4S isomers of cementum versican was approximately 7:1. Furthermore, these PGs were immunolocalized in and around tooth cementum using antibodies generated against the respective core proteins. Intensive immunostaining for versican was found almost exclusively in the lacunae housing cementocytes in cementum and osteocytes in alveolar bone, respectively. Immunostaining for decorin was mainly associated with collagen fibers in the periodontal ligament and slightly in cementum matrix, while the one for biglycan was mainly in cementoblasts/precementum. These differential tissue distributions of the CSPGs suggest that they may play distinct roles in cementogenesis.

Animals↗
PubMed1999

Detection of mammosomatotrophs in paraffin-embedded specimens of various pituitary adenomas.

BACKGROUND: There are various classification systems for pituitary adenomas based on whether mammosomatotroph cells, which simultaneously express both prolactin (PRL) and growth hormone (GH), can be found. Until the present, the identification of such cells required special techniques and could not be performed in paraffin-embedded specimens. This hindered large-scale studies for detection of mammosomatotrophs in various pituitary adenomas and, as a result, such classification has remained controversial. To establish a methodology for the detection of mammosomatotrophs in paraffin-embedded specimens and to propose a more logical classification for pituitary adenomas, the authors conducted this retrospective study. METHODS: We performed double immunofluorescence staining of PRL and GH in paraffin-embedded specimens of various pituitary adenomas with subsequent observation with a confocal laser-scanning microscope. RESULTS: Mammosomatotrophs were found in four of the 10 GH-secreting adenomas and one of the 10 clinically nonfunctioning adenomas. However, mammosomatotrophs were not identified in all 10 cases of prolactinoma. CONCLUSIONS: This is the first report in the literature that successfully demonstrates the presence of mammosomatotrophs in routine paraffin-embedded pituitary adenomas. The new methodology is important for future study of the function and role of these cells. A large-scale study for mammosomatotrophs in various pituitary adenomas with this method and a more logical classification of pituitary adenomas are proposed.

Adenoma↗
PubMed1999

[Experimental study and preliminary clinical application of bacterial collagenase in catabolizing scars].

OBJECTIVE: To investigate the mechanism of collagenase in degradation of hypertrophic scars and observe the clinical effects of this therapy. METHODS: Both animal experiment and clinical trial were conducted. RESULTS: The injection of collagenase into the hypertrophic scar tissues in nude mice resulted in 86% volume reduction after two injections within two weeks, while the control tissues reduced only by 35% during the same time. Clinically, 13 cases were treated with intralesional injection of bacterial collagenase. The volume reduction rate was 46.92% in average within two weeks. The volume reduction in 4 of 13 cases was above 50%. Three to sixteen months' follow-up of five patients revealed that only one case of keloid recurred after treatment in the second month. Examinations of histological sections and TEM showed the dissolved collagen fiber clearly. CONCLUSION: Collagenase can degrade collagen fiber directly. The prompt significant effects and the mild complications make it a prospective therapy.

Adolescent↗
PubMed1999

[Relationship of polymorphism of LMP2 gene to insulin-dependent diabetes mellitus and DR3 gene].

OBJECTIVE: To investigate the relationship of polymorphism of large multifunctional protease (LMP) 2 genes to insulin-dependent diabetes mellitus (IDDM) and DR3 gene. METHODS: The polymorphism of LMP2 genes was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 68 IDDM patients and 71 healthy controls. IDDM patients and healthy controls were respectively divided into 2 groups according to DR3 genotyping. One group included subjects with DR3 gene, and another group subjects without DR3 gene. RESULTS: In the subjects with DR3 gene, the frequencies of LMP2-R/H, LMP2-R/R, LMP2-H/H were 47%, 47% and 6% in the IDDM patients, 13%, 87%, 0% in the controls. Compared with the Controls, the IDDM patients had a higher frequency of LMP2-R/H (P < 0.05) and a lower frequency of LMP2-R/R (P < 0.05). In the subjects without DR3 gene, the frequencies of LMP2-R/H, LMP2-R/R, LMP2-H/H were 58%, 39%, 2.8% respectively in the IDDM patients, and 32%, 54%, 14% respectively in the controls. Compared with the controls, the IDDM patients had a higher frequency of LMP2-R/H (P < 0.05), the frequency of LMP2-R/R in the IDDM patients did not have a significant difference from that in the controls (P > 0.05). CONCLUSIONS: There may be a significant association of LMP2-R/H and LMP2-R/R with the susceptibility to IDDM. The LMP2-R/H is a susceptible gene. The people with LMP2-R/H have a higher risk of suffering from IDDM. The LMP2-R/R is a protective gene. The people with LMP2-R/R have a decreased risk of suffering from IDDM. The effects of LMP2 on ID-DM are not affected by DR3 gene.

Cysteine Endopeptidases↗
PubMed1999

[Inquiring the causes of recurrence of hepatocellular carcinoma after surgical resection].

OBJECTIVE: To analyze the causes of recurrence of hepatocellular carcinoma (HCC) after resection according to pathologic findings of the resected primary tumor and angiographic features of the recurrent tumor. METHODS: In this series, 142 cases with recurrent HCC were analyzed with respect to (1) size, number, gross and histologic findings of the primary tumor, (2) time when recurrence occurred, (3) size, number, blood supply, staining property of, and deposition of lipiodol oil in the recurrent tumor. Following angiography, arterial embolization was performed. RESULTS: In 101 of the 142(71.1%) cases, the primary tumor was > 5 cm in diameter, and in 41 cases (28.9%) it was < 5 cm. In 67.7% of the cases, the capsule of the primary tumor was incomplete or absent. In 47 cases (33.1%), satellite tumor nodules were seen during operation but they were seen on pathologic sections in 94 cases (66.2%). Tumor thrombus was present in the portal vein in 26 (18.3%) and 121 cases (85.2%) during operation and on pathologic examination, respectively. In the majority of the cases (99/142), recurrence occurred within 6 months after operation. The recurrent foci consisted of multiple tumor nodules of < 5 cm in 68.3% of the cases. On angiography, the recurrent tumors were rich in blood supply with good deposition of lipiodol. CONCLUSION: Recurrence is apt to occur in HCC patients with large (> 5 cm) primary tumor which has incomplete or no capsule, satellite tumor nodules and portal vein tumor thrombus. It is suggested to perform angiography 1-2 months after surgery to detect early recurrence and, if confirmed, the patients can be treated by transcatheter arterial chemo-embolization.

Adult↗
PubMed1999

[A methodological study on the evaluation of insulin resistance in vivo].

OBJECTIVE: To investigate the advantage and disadvantage of several methods often used to evaluate insulin resistance and to attempt to modify the disadvantage. METHODS: Three protocols of minimal model technique (MMT), three protocols of basal state approach and four protocols of oral glucose tolerance test (OGTT) were used respectively to calculate insulin sensitivity index (ISI) in 16 subjects with normal glucose tolerance (NGT) and 13 patients with non-insulin-dependent diabetes mellitus (NIDDM). ISI of classical MMT was regarded as standard; ISI of other protocols were analyzed, assessed and compared with that of classical MMT. RESULTS: Except the ISI expressed by the ratio of fasting serum glucose to insulin concentration (FSG/FIns) and the ratio between area under curve (AUC) of glucose and insulin (AUCg/AUCi) in OGTT, ISI of other protocols was significantly higher in NGT group than in NIDDM group (P < 0.05, ISI relative values were 1 and 0.44 - 0.70 respectively) and had stronger relationships as compared with ISI of classical MMT (r = 0.45 - 0.92, P < 0.05). CONCLUSION: The modifications that reduce the samples to 12 or 10 and shorten the time to 120 min for MMT are feasible. Both the homeostasis model assessment and the basal state method designed by LI Guangwei are very simple; they can roughly evaluate insulin sensitivity. OGTT designed by Cederholm is a relatively simple and precise method of measuring IR. Two protocols of OGTT designed by the authors may be accurate methods for evaluating IR. Both FSG/FIns and AUCg/AUCi can not reliably evaluate insulin sensitivity.

Adult↗
PubMed1999

[An experimental method for measuing flexor pulley's mechanical effects by imitating hand in vivo].

Flexor pulley system has an important mechanical effect on digital flexion function. An experimental method was designed to measure the pulleys' mechanical effects by using hand in vitro to imitate hands in vivo. The pulleys' function was evaluated by pulley incision and pulley preservation, and percentage loss of work was used as an index. The results demonstrate that this experiment is reasonable in design and methodology.

Adult↗