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Biomedical subjects

G Yang

Publications and source records attributed to G Yang.

At least 379 records · Page 21Linked to original sources

DNA ploidy and clonal selection in ras + myc-induced mouse prostate cancer.

An important goal in prostate cancer research is to define specific molecular and cellular alterations that are associated with malignant progression. The mouse prostate reconstitution model is a relevant and useful system as it allows the study of early events in cancer progression under conditions where oncogene-initiated cells are surrounded by normal tissue. Using this model, activated ras and myc oncogenes are introduced into urogenital sinus cells via the recombinant retrovirus Zipras/myc 9. After 4 weeks' growth as subcapsular renal grafts, poorly differentiated carcinomas are produced in C57BL/6 mice. In this study we examined the temporal relationships between morphological alterations, growth, DNA ploidy status and clonal selection as determined by Southern blotting in ras + myc-initiated carcinomas. Nuclear image analysis demonstrated that the emergence of a cycling DNA tetraploid cell population strongly correlated with growth and histologic progression. These tightly linked events culminated in the outgrowth of mono- or oligoclonal cancer.

Animals↗

The frequency of apoptosis correlates with the prognosis of Gleason Grade 3 adenocarcinoma of the prostate.

BACKGROUND: Although localized carcinomas are predominantly moderately differentiated (Gleason Grade 3), they demonstrate markedly different rates of progression. Previously, the authors reported a correlation between apoptosis and the malignant characteristics of carcinoma in the mouse prostate reconstitution model system and between apoptosis and Gleason grade in the human tumor. This study was undertaken to determine whether the frequency of apoptosis correlates with prognosis and to compare the prognostic significance of the apoptotic index with other prognostic features in Gleason Grade 3 carcinomas. METHODS: The apoptotic and mitotic indices of malignant and nonmalignant epithelium in 28 consecutive radical prostatectomy specimens were determined for a carcinomas composed entirely of Gleason sum 6 (primary Grade 3, secondary Grade 3) with a clinical stage T2 classification. Each patient was followed for 5-9 years (median 6, years). The indices, defined as the number of apoptotic and mitotic bodies in an H & E-stained section per 100 grids delineated by an ocular measuring field, were determined. The actuarial time to progression, defined as a sustained rise in the serum prostate specific antigen level greater than or equal to 0.4 ng/ml, was correlated with the apoptotic index, the mitotic index, tumor volume, and pathologic stage. RESULTS: Neither pathologic stage nor tumor volume differed significantly between the group of 19 patients (68%) with no progression and the other 9 whose tumor progressed. The median apoptotic index of the carcinomas was 0.87 (range, 0.12-3.91). For patients with a low apoptotic index (< 0.87), the actuarial progression rate at 5 years was 7% +/- 14% (+/- 2 SE) compared with 50% +/- 26% for those with a high apoptotic index (P < 0.007). Mitotic index had no prognostic significance. CONCLUSIONS: In carcinoma of the prostate, apoptosis can be recognized in standard H & E sections and quantitated by light microscopy. The apoptotic index may provide additional prognostic information in the predominant grade of early stage carcinoma. Cancer 1995; 75:522-9.

Adenocarcinoma↗

Therapeutic considerations in patients with refractory neurosarcoidosis.

OBJECTIVE: To assess the effectiveness of alternative treatments for patients with refractory neurosarcoidosis. DESIGN: Nonrandomized, retrospective patient survey. SETTING: Multicenter, involving patients cared for by their primary physicians and neurologists, and referred for management advice to a neurology consultant. INTERVENTIONS: Patients were treated with corticosteroids and alternative treatments, including azathioprine, cyclosporine, cyclophosphamide, chlorambucil, methotrexate, and radiation therapy. RESULTS: Prednisone dosage was successfully tapered to 10 to 20 mg/d without worsening symptoms in 10 (38%) of the 26 patients studied. Six (23%) patients had improved conditions while receiving alternative medication and nine (35%) patients' conditions remained stable with no further progression of their symptoms. Radiotherapy was beneficial for one of three patients. Four (15%) patients did not respond to alternative treatment and died of worsening symptoms or infection. Adverse effects of the alternate medications resolved on discontinuing treatment with the offending agent. CONCLUSION: Alternative treatment is an effective adjunct to corticosteroid therapy for some patients with refractory neurosarcoidosis. Clinical deterioration may occur despite combined therapy. Choice of alternative therapy should be determined, in part, by its potential adverse effects.

Adult↗

Determination of amino acids by on-line capillary electrophoresis-electrospray ionization mass spectrometry.

On-line capillary electrophoresis-electrospray ionization mass spectrometry (CE-ESMS) has been used for the separation and detection of amino acid mixtures. Four natural amino acids, histidine, tryptophan, phenylalanine, aspartic acid, and a tripeptide, glutathione, were separated and determined. Protonated molecules were detected in the CE-ESMS mode with detection limits of about one pmol. Optimum CE-ESMS operating conditions for amino acid analysis were determined employing acetic acid solutions as CE electrolytes. The examined parameters included capillary diameter (50-100 microns internal diameter), applied separation voltage (20-30 kV), and concentration of electrolyte (10-60% acetic acid). Stable working conditions were maintained when the CE currents were less than 18 microA. The use of electrolyte solutions such as those described here instead of true buffer solutions may have advantages for CE-ESMS systems which employ a "sheathless" interface.

Amino Acids↗

Transforming growth factor-beta localization during mouse prostate morphogenesis and in prostatic growth abnormalities.

Growth and morphogenesis of the prostate involves mesenchymal-epithelial interactions. Transforming growth factor-beta 1 (TGF-beta1) is one growth factor that may play a role in these paracrine interactions. We have localized TGF-beta1 by molecular and immunohistochemical analysis in the developing mouse prostate. Accumulations of TGF-beta1 protein were localized in the mesenchyme surrounding ductules in fetal and neonatal prostate. Previous studies in the mouse prostate reconstitution (MPR) model system have localized accumulations of TGF-beta1 to regions of oncogene-induced abnormalities. In surgically excised adult human prostate tissues, localized accumulations of TGF-beta1 are associated with prostate cancer and benign prostatic hyperplasia (BPH). Intracellular TGF-beta1 was more often associated with stromal cells in BPH and with neoplastic epithelial cells in prostate cancer. The production and accumulation of TGF-beta1 appears to involve interactions between mesenchymal and epithelial cells. Further experimental studies may clarify the relationships between TGF-beta1 and abnormal prostatic growth.

Animals↗

Transgenic mice and knockout mutants in the study of oxidative stress in brain injury.

A rapid increase in the need to explore the molecular basis of cellular function and injury in the central nervous system has led neuroscientists to employ transgenic mouse technology. The successful making of transgenic mice (Tg) overexpressing human CuZn-superoxide dismutase (SOD-1) activity has made it possible to investigate the role of oxygen free radicals in ischemic and traumatic brain injury in a molecular fashion. It has been demonstrated that the 3-fold increase in SOD-1 transgene activity in SOD-1 Tg mice offers protection against cerebral ischemia and reperfusion in two different models of focal cerebral ischemia, as compared to nontransgenic wild-type littermates. Studies involving traumatic brain injury have also demonstrated that acute injuries, including brain edema and blood-brain barrier permeability, are significantly reduced in SOD-1 Tg mice. Furthermore, chronic neurological deficits, such as beam walking, beam balance, and body weight, are significantly improved in these transgenic animals following traumatic brain injury. In addition to the SOD-1 Tg mice being a useful tool for the study of CNS injury, targeted disruption of the mouse gene for mitochondrial manganese SOD (SOD-2) has been successful. These SOD-2 knockout mutant mice, in addition to the recently developed knockout mutants of neuronal nitric oxide synthase (NOS), are believed to offer a unique opportunity to elucidate the oxidative mechanisms in brain injury following stroke and trauma.

Animals↗

Interstitial deletion of the endothelin-B receptor gene in the spotting lethal (sl) rat.

The autosomal recessive spotting lethal (sl) rat phenotype is characterized by absence of intramural ganglion cells in the entire colon and distal small bowel, thus resembling the human Hirschsprung (HSCR) disease. A strategy for identifying the gene responsible for this rat defect was initiated by backcrossing DA x sl rats. After excluding linkage with two candidate genes, RET and Endothelin-3 (EDN3), a highly significant lod score (Z = 47.05 at theta = 0) was found between the Endothelin-B Receptor (EDNRB) gene and the sl phenotype. The exon-intron structure of this rat gene was reconstructed and each exon of the sl rat was screened for possible mutations. A 301 bp interstitial deletion, encompassing the distal half of the first coding exon (exon 2) and the proximal part of the adjacent intron, was demonstrated. This deletion results in two transcriptional products, 270 and 238 bp shorter than wild type cDNA. The discovery of the molecular defect underlying the sl rat phenotype should contribute to the understanding of the genetic heterogeneity of HSCR in man.

Animals↗

Transgenic animals in the study of blood pressure regulation and hypertension.

It is generally accepted that the etiology of essential hypertension is due to a complex interplay of genetic and environmental factors. A great deal of research effort over the past ten years has been focused on the identification of genes the variants of which predispose individuals to high blood pressure. Consequently, transgenic and knockout animals have become important research tools, providing experimental systems in which defined genetic manipulations can be introduced on uniform genetic backgrounds while minimizing environmental variation. These animal models have provided the means by which candidate genes thought to be involved in blood pressure regulation have been studied. Furthermore, these models can be used to test the significance of genes and gene variants identified via genome-wide searches as potential causes of hypertension. The purpose of this review is to provide a brief discussion of transgenic and knockout methodology and its application to study the genetic basis of hypertension.

Angiotensinogen↗

Endogenous human renin expression and promoter activity in CALU-6, a pulmonary carcinoma cell line.

We have previously reported that transgenic mice containing the human renin gene express high levels of human renin mRNA in the lung. We show in this report that human renin expression in two lines of transgenic mice is developmentally regulated. Human renin expression is not evident in the transgenic mouse lung at 15.5 days of gestation, is detectable at 17.5 days of gestation, peaks around birth, and remains elevated into adulthood. In situ hybridization of mouse fetal lung samples at 18.5 days of gestation revealed that human renin was exclusively expressed in pulmonary type II epithelial cells. A survey of the medical literature revealed a number of clinical cases in which hypertension was caused by renin-secreting pulmonary tumors and a fairly widespread occurrence of immunoreactive renin in banked pulmonary tumors of diverse origin. This prompted us to examine a number of pulmonary tumor cell lines to determine whether they express human renin mRNA. One pulmonary carcinoma cell line, CALU-6, expressed human renin mRNA endogenously. Human renin expression in these cells was induced approximately 100-fold after treatment with forskolin, 8-bromoadenosine 3':5'-cyclic monophosphate, or N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate. Transfection analysis of human renin promoter-luciferase fusion constructs revealed the presence of cell-specific positive and negative regulatory elements in the human renin 5'-flanking DNA. This cell line is the only immortalized human cell line that expresses high levels of endogenous human renin mRNA and should provide an excellent tool for studying the regulation of human renin expression in vitro.

Animals↗

[Effect of scopolamine on the contents of beta-endorphin and oxytocin in hypothalamus, pituitary and plasma in morphine dependent rats].

Male Sprague-Dawley rats weighing 180-220 g were rendered dependent on morphine by repeated injections of morphine in increasing doses for 14 days. 0.3 mg/kg of scopolamine was injected intraperitoneally bid for 3 and 4 days. Control rats were similarly injected with saline. The contents of beta-endorphin (beta-EP) and oxytocin (OT) in hypothalamus, pituitary and plasma were measured by radioimmunoassay. The results showed that both beta-EP and OT in hypothalamus and plasma increased but both were decreased in pituitary in morphine dependent rats (P < 0.01). After scopolamine treatment, the contents of beta-EP increased but OT decreased in hypothalamus (P < 0.01), and both elevated significantly in pituitary (P < 0.01). The results suggested that scopolamine might modulate hypothalamus-pituitary system to affect the release or synthesis of beta-EP and OT in the brain.

Animals↗

Controlling cancerous pain with analgesic powder for cancers.

Analgesic powder for cancers, composed of more than 20 Chinese drugs, was applied externally to 91 patients with various kinds of cancers for management of cancerous pain. The results showed that it was remarkably effective in 42 cases, fairly effective in 22, effective in 22, and ineffective in 5, the total effective rate being 94.51%. Animal experiments indicated that the pain threshold was evidently higher in mice treated with this powder on the site of femoral artery of the hind limbs than that of the controls without application of this powder.

Administration, Cutaneous↗

Ultrastructural cytochemistry of human gastric cancer: electron microscopic observations of five organellae marker enzymes.

The distribution of ALPase, ACPase, G6Pase TPPase and CCOase of gastric cancer and normal gastric epithelium were studied ultrastructurally. The results showed that normal gastric epithelium had no ALPase reaction. The reactions of ACPase, G6Pase, TPPase and CCOase were found in the corresponding organellae which were consistent with their functions. In tubular adenocarcinoma cells, their reactions were more apparent in the corresponding organellae. Some cells of tubular adenocarcinomas showed ALPase reaction. The mucinous adenocarcinoma cells had higher ACPase and TPPase reactions. In poorly differentiated adenocarcinoma cells, the five marker enzymes showed negative or faint reactions. The biological significance and mechanisms of distribution of the five marker enzymes were discussed.

Acid Phosphatase↗

Diffusion-weighted magnetic resonance imaging during brief focal cerebral ischemia and early reperfusion: evolution of delayed infarction in rats.

The purpose of this study was to ascertain if the signal intensity ratio and the lesion area determined by diffusion-weighted magnetic resonance imaging during brief focal ischemia and early reperfusion predict outcome determined by diffusion-weighted magnetic resonance imaging and T2-magnetic resonance imaging at 24 h. Seventeen rats were imaged before and during 30 min of endovascular middle cerebral artery occlusion and at 15 min, and 23.5 h after the onset of reperfusion. Both hemisphere and basal ganglia signal intensity ratio increased significantly from baseline during ischemia, decreased significantly from ischemic levels during early reperfusion, and increased again at 24 h. However, signal intensity ratio during ischemia or after 45 min of reperfusion did not correlate statistically with diffusion-weighted-signal intensity ratio at 24 h. Both hemisphere signal intensity ratio and basal ganglia signal intensity ratio at 15 min of reperfusion correlated, but only moderately, with diffusion-weighted-signal intensity ratio at 24 h (r = 0.52, p < or = 0.05). Although lesion areas during ischemia were comparable to those observed at 24 h, lesion areas at both 15 and 45 min of reperfusion were significantly smaller than those observed during ischemia and at 24 hr. Thus, sequential imagining demonstrated partial resolution and delayed recurrence of magnetic resonance-defined ischemic lesions during reperfusion after brief focal ischemia.

Animals↗

[Adrenocortical carcinoma: report of 20 cases].

The authors reported 20 cases of adrenocortical corcinoma. The tumors were nonfunctional in 12 cases (average age 49.7) and functional in 8 cases (5 with hypercortisolism, 3 with adrenogenital syndrome; average age 8.8). The prognosis in this group were poor, the survival of one year was 40%, two years 35% and five years 10%. Most of adrenocortical carcinomas in childhood were functional and their prognosis were poor because of delayed treatment. The nonfunctional tumors were usually diagnosed in the late period, therefore the prognosis was worse, but in recent years some cases of no secretory carcinomas had been occasionally found by image diagnosis and these tumors were small, so their prognosis was favorate.

Adenocarcinoma↗