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Biomedical subjects

T Lei

Publications and source records attributed to T Lei.

At least 19 recordsLinked to original sources

Effect of 17 beta-estradiol on the brain damage and metabolic changes in rats.

An in vivo model of glutamate excitotoxicity in which glutamate is applied to the cortex of rats through a microdialysis probe has been used to investigate the neuroprotective processes initiated by 17 beta-estradiol. Rats were pre-treated with 17 beta-estradiol i.v. before local application of glutamate. The experimental results showed that pre-treatment with 17 beta-estradiol significantly reduced the size of the glutamate-induced lesion. In the microdialysates, the peak of lactate observed immediately after glutamate application was significantly higher and longer lasting after 17 beta-estradiol pre-treatment. The level of extracellular glucose was markedly decreased concomitantly to the increase in lactate, but no difference could be observed with and without 17 beta-estradiol pre-treatment. These suggest a new neuroprotective mechanism of 17 beta-estradiol by activating glutamate-induced lactate production. This effect on lactate production and lesion reduction is estrogen receptor dependent and is abolished totally by estrogen antagonist tamoxifen. It was also demonstrated here that high lactate subserves estrogen neuroprotection during glutamate toxicity.

Animals↗

A sensor array processing approach to object region detection.

This paper presents a new approach for medical image analysis. It translates the object region-detection problem into a sensor array processing framework and detects the number of object regions based on the signal eigenstructure of the converted array system. The theoretical and experimental results obtained by using this approach on various medical images were in good agreement.

Biomedical Engineering↗

Artery-vein separation via MRA--an image processing approach.

This paper presents a near-automatic process for separating vessels from background and other clutter as well as for separating arteries and veins in contrast-enhanced magnetic resonance angiographic (CE-MRA) image data, and an optimal method for three-dimensional visualization of vascular structures. The separation process utilizes fuzzy connected object delineation principles and algorithms. The first step of this separation process is the segmentation of the entire vessel structure from the background and other clutter via absolute fuzzy connectedness. The second step is to separate artery from vein within this entire vessel structure via iterative relative fuzzy connectedness. After seed voxels are specified inside artery and vein in the CE-MRA image, the small regions of the bigger aspects of artery and vein are separated in the initial iterations, and further detailed aspects of artery and vein are included in later iterations. At each iteration, the artery and vein compete among themselves to grab membership of each voxel in the vessel structure based on the relative strength of connectedness of the voxel in the artery and vein. This approach has been implemented in a software package for routine use in a clinical setting and tested on 133 CE-MRA studies of the pelvic region and two studies of the carotid system from six different hospitals. In all studies, unified parameter settings produced correct artery-vein separation. When compared with manual segmentation/separation, our algorithms were able to separate higher order branches, and therefore produced vastly more details in the segmented vascular structure. The total operator and computer time taken per study is on the average about 4.5 min. To date, this technique seems to be the only image processing approach that can be routinely applied for artery and vein separation.

Algorithms↗

[Current evolution of plasma sprayed hydroxyapatite coating].

The present attempt is to briefly review the processing and properties of plasma sprayed hydroxyapatite coatings in terms of characteristics of hydroxyapatite ceramics, plasma spraying technology, titanium-ceramic interfacial cracking and component designing of hydroxyapatite coating based composite. The coating is a weak part in implant system. The main purpose of research on plasma spraying technology and component designing is to improve coating integrality and coating-matrix adhesion strength. Functionally gradient materials can provide a new route to solve the above two problems.

Biomechanical Phenomena↗

[Colon cancer risk factors in Jiashan county, Zhejiang province, the highest incidence area in China].

OBJECTIVE: To investigate the risk factors of colon cancer in the highest incidence area, Jiashan county, providing scientific basis for monitoring and prevention. METHODS: With a population-based case-control study, 109 colon cancer patients with 1:7 matched controls were interviewed with uniform questionnaires. Conditional logistic regression was used for univariate and multivariate analysis of colon cancer. RESULTS: Ten years before, high monthly pork consumption (OR = 1.608), high monthly animal oil consumption (OR = 1.391), psychological depression (OR = 9.887), negative emotion (OR = 1.723), lower digestive tract diseases (OR = 4.163), and history of colorectal cancer in the first degree relatives (OR = 3.421) were the main risk factors of colon cancer. At that time, high monthly vegetable consumption was a protective factor for colon cancer (OR = 0.422). CONCLUSION: Colon cancer in Jiashan county was related to dietary factors. The research results support the colon cancer etiological hypothesis of "fat-bile acid" and "deficiency of dietary fibres". Psychological depression, inheritance and lower digestive tract diseases were also correlated with colon cancer.

Case-Control Studies↗

Clinical and biochemical characteristics of growth hormone-secreting pituitary tumors.

To investigate the difference of biochemical characteristics on gsp-positive and gsp-negative growth hormone (GH)-secreting pituitary tumors, 18 GH-secreting pituitary tumors were examined for their clinical characteristics and gsp oncogenes. All patients received the pituitary function combinative stimulating test. It was found that there were no difference in the sex, age, tumor size, course of disease and plasma basal GH levels with gsp-positive and gsp-negative patients. The plasma levels of PRL were increased in most patients (11/18), and the plasma levels of TSH in gsp-positive patients were higher than those in gsp-negative patients (P < 0.05). There was no significant difference in the responses to pituitary combinative stimulating test in gsp-positive and gsp-negative patients. It was concluded that there was little difference in the clinical biochemical characteristics of gsp-positive with gsp-negative GH-secreting pituitary tumors.

Adult↗

Preliminary study on the relationship between cAMP level and gsp expression in cultured human pituitary somatotrophinomas.

In order to investigate the relationship between abnormal intracellular signal transduction and tumorgenesis of human pituitary somatotrophinomas, the effects of protein kinase A (PKA)-dependent growth hormone (GH) releasing hormone (GHRH) and protein kinase C (PKC)-dependent GH-releasing peptide (GHRP-6) on cAMP production were observed by using cell culture and biochemical methods, and the expression of the gsp oncogene was detected by using PCR and direct sequence assay methods in 11 patients with human pituitary somatotrophinomas. It was found that GHRP-6 exerted significant stimulatory effect on cAMP production by 2 gsp-positive tumors and no effect on the gsp-negative tumors. GHRP-6 could enhance the stimulation of cAMP production induced by GHRH in tumor without gsp oncogenes. It was suggested that both GHRH and GHRP-6 exert identical effects on human pituitary soamtotrophinomas, which was contributed to the cross-talk between the two intracellular signal transduction pathways in pituitary cells.

Adenoma↗

The regulatory effects of protein kinase C on the proliferation of cultured human low-passage meningioma cells.

The potential role of the protein kinase C (PKC)-mediated signal transduction pathways in growth regulation was evaluated and the effects and the possible mechanism of PKC inhibitor on low-passage human meningioma cells in vitro investigated. Freshly resected meningiomas obtained from the operation were placed into cell cultures. Cells from early-passage were used for the following experiments. The numbers of the cultured meningioma cells were counted to evaluate the effect of the PKC inhibitor staurosporine on proliferation of meningioma cells. The basal phosphatidylinositol (PI) turnover rate and the inhibitory rate of starosporine on the proliferation of the meningioma cells were detected. It was found that the proliferation of the low-passage human meningioma cells was inhibited by staurosporine in a dose-dependent manner. The inhibitory rate of staurosporine was positively correlated with the basal PI turnover rate (r = 0.58, P < 0.01). It was suggested that PKC-mediated signal pathway is involved in the proliferation of the low-passage human meningioma cells. The procedure that PKC regulated the proliferation of human meningioma cells is a complex procedure. It is necessary to make more research in order to explore a non-operation therapy or an adjuvant therapy.

Cell Division↗

Interaction of the novel GH secretagogue hexarelin with GHRH in regulating the secretion of GH by cultured human pituitary somatotrophinomas in vitro.

The effects of the novel GH-releasing hexapeptide, Hexarelin, on the secretion of GH in cultured human pituitary somatotrophinomas was further investigated. Hexarelin (20 nmol/L) strongly stimulated GH secretion, which could be reduced by phloretin, but not by RP-cAMPS, an inhibitor of protein kinase A (PKA). (Ac-Tyr1,D-Arg2)-GRF(1-29)-NH2 failed to block the effects of Hexarelin but completely abolished the stimulation of GH secretion exerted by GHRH. When added alone to somatotrophinoma cell cultures, Hexarelin had no effect on cAMP levels, but it potentiated the stimulatory effects of GHRH. These results demonstrated that Hexarelin could directly stimulate GH secretion by human pituitary somatotrophs PKC-dependently, which might be contributed to the activation of the PI transduction system. In addition, Hexarelin could interact with GHRH on the adenylyl cyclase system.

Adenoma↗

The role of protein kinase C and its effect on GHRH in the regulation of hormone secretion by somatotrophinomas.

Phorbol ester-induced release of growth hormone (GH) and prolactin (PRL) from human somatotrophic tumors was examined in vitro. 12-O-tetradecanoyl-phorbol-13-acetate (TPA) strongly stimulated GH and PRL secretion and showed an additive effect on GH secretion if used in combination with GH releasing hormone (GHRH). In contrast, staurosporine exerted a variable inhibitory effect on GH release. There was no correlation between such effects and gsp mutations. The findings suggested that TPA doesn't act directly through cAMP signal transduction system.

GTP-Binding Protein alpha Subunits, Gs↗

The effect of GHRH, GHRP-2 and somatostatin on GH secretion by fetal pituitary.

Growth hormone releasing peptide (GHRP-2) is a synthetic hexapeptide which specifically stimulates secretion of growth hormone (GH) by fetal pituitary somatotrophs through a new membrane receptor, which is different from growth hormone releasing hormone (GHRH) and somatostatin (SMS) receptors. We used cell cultures of human fetal pituitary somatotroph cells to investigate the effect of GHRH, GHRP-2 and somatostatin on GH secretion. The results showed that the mechanism of GHRH/SMS and GHRP-2 was different. This indicated that a different intracellular signal transduction system might also play a crucial role in the regulation of GH secretion.

Fetus↗

Effects of the novel GH secretogogue, hexarelin on GH secretion and phosphatidylinositol hydrolysis by human pituitary somatotrophinomas in cell culture.

The effects of the novel GH-releasing hexapeptide, Hexarelin, on cultured human pituitary somatotrophinomas were investigated. Hexarelin (0.01-100 nmol/L) dose-dependently stimulated GH secretion up to 4.6-fold. Maximal effects occurred with 10 nmol/L. These effects were very similar to those observed with GHRP-6. The effects of Hexarelin were reduced by phloretin, an inhibitor of protein kinase C (PKC). The rate of phosphatidylinositol (PI) hydrolysis was markedly increased by Hexarelin in a dose-dependent manner. These results demonstrated that Hexarelin could directly stimulate GH secretion by human pituitary somatotrophs in a PKC-dependent manner, probably via activation of the PI transduction system.

Adenoma↗

TPA enhances growth hormone (GH) secretion effect of GH-releasing hormone (GHRH) by human gsp-positive pituitary somatotrophinomas.

In recent years, one of the most exciting advances in the researches of pituitary adenomas is the discovery that 30%-40% of human pituitary somatotrophinomas carry somatic mutations of the gene for the alpha-subunit of the stimulatory GTP-binding protein, Gs (Gs alpha). These mutations, termed gsp oncogenes, may play an important role in the tumorigenesis of pituitary adenomas. Of 10 somatotrophinomas examined, 3 (30%) were proved to be gsp positive, as determined by sequence analysis of DNA generated by the polymerase chain reaction (PCR). GHRH exerted a significant stimulatory effect on GH secretion in 2 of 3 gsp-positive and 4 of 7 gsp-negative tumors. Moreover, phorbol ester, 1, 2-tetradecanoylphorbol-13-acetate (TPA), enhanced stimulation of lated the GH secretion effect exerted by GHRH in gsp-positive somatotrophinomas, whereas this effect was not observed in gsp-negative tumors. This result suggests that the protein kinase C signal system as well as adenylyl cyclase-cAMP-protein kinase A intracellular signal transduction system plays a pivotal role in GH secretory control of GHRH, which may work together via a cross-talk mechanism.

Adenoma↗

Hormone secretion by cell culture of human GH-PRL secreting pituitary adenomas: effects of bromocriptine.

Dopamine agonists effectively reduce the secretion of prolactin (PRL) in the great majority of prolactinomas and reduce the bulk of the adenomas, as well as have partial therapeutic effect on some patients with acromegaly. The inhibitory effect of bromocriptine (BC), a dopamine agonist, on growth hormone (GH) and PRL secretion of dispersed cells from the pituitary adenomas of 16 cases of acromegaly, which secret GH and PRL simultaneously, were evaluated in vitro. The significant inhibitory effects of BC on PRL secretion were found in 12 cases. It was also found that PRL secretion was strongly inhibited when GH was suppressed; on the contrary, when GH secretion was not suppressed, the production of PRL was not or weakly inhibited. The exact mechanism of the effects is unclear so far. It is necessary to investigate, at molecular level, the etiology of GH-PRL adenomas and its response to therapeutic agents.

Adenoma↗

Overexpression of stimulatory G protein alpha-subunit is a hallmark of most human somatotrophic pituitary tumours and is associated with resistance to GH-releasing hormone.

The heterotrimeric Gs protein-adenylyl cyclase (AC) cascade plays a pivotal role in controlling hormone secretion by endocrine glands. Consequently, deficiency of the alpha-subunit of Gs leads to endocrine hypofunction and hypoplasia in the affected cells whereas AC hyperactivity results from activating point mutations within the Gs-alpha gene. The latter, termed gsp oncogenes, are found primarily in a subset of growth hormone (GH)-secreting human pituitary tumours (somatotrophinomas) and are thus associated with excessive GH secretion. We present here evidence that another type of defect in human somatotrophinomas may be overexpression of the Gs-alpha subunit. Immunohistochemistry using an antibody against recombinant human Gs-alpha revealed high levels of expression in 25 of 39 somatotrophinomas but weak staining in normal human pituitary cells. These results were confirmed by Western blot analysis. Additionally, cholera toxin-mediated ADP-ribosylation in the presence of 32P-labelled NAD+ resulted in an autoradiographic signal intensity which correlated directly with magnitude of immunostaining and amount of antigen shown by Western blot analysis, providing evidence for overexpression of functionally active subunit. Finally, reconstitution assays were applied and directly demonstrated the increased activity of overexpressed Gs-alpha. In vivo, the effect of Gs-alpha on AC activity may be partially counterregulated by high levels of inhibitory G protein that also occurred in these tumours. In culture, GH-releasing hormone (GHRH) had markedly reduced effects on GH secretion by somatotrophinomas exhibiting Gs-alpha overexpression, whereas powerful stimulation occurred in weakly staining tumours. In contrast to these observations with Gs-alpha, immunostaining for the phospholipase C-coupled G11-alpha subunit was relatively weak in all somatotrophinomas studied and synthetic GH-releasing peptide, which acts via a specific G11-coupled receptor, led to powerful and consistent stimulation of GH secretion by different tumours. These results indicate that Gs-alpha overexpression is associated with dysfunction in hormone secretion by some somatotrophinomas.

Adenoma↗

Relationship between invasiveness of pituitary somatotrophinomas and structural abnormalities of protein kinase C gene in human.

The potential role of the protein kinase C (PKC) transduction system in controlling proliferation of human pituitary somatotrophinomas was investigated. Twenty somatotrophinomas were studied using PCR and direct sequencing methods. No point mutation within the alpha PKC gene, previously thought to be associated with invasive pituitary tumors, was found in any of the 20 somatotrophinomas. It is concluded that PKC transduction system may play an important role in controlling pituitary somatotrophinoma proliferation, but there is no correlation between invasiveness and the previously reported alpha PKC gene mutation.

Adenoma↗

Relationship between GHRP-6 and TPA in the regulation of growth hormone secretion by human pituitary somatotrophinomas.

Growth hormone releasing peptide (GHRP-6) is a synthetic hexapeptide which specifically stimulates secretion of growth hormone (GH) by pituitary somatotrophs. Phorbel ester, 1, 2 tetradecanoylphorbol 13 acetate (TPA) can also stimulate releasing of GH. The precise intracellular mechanism has not been entirely deciphered. We used cell cultures of human pituitary somatotrophinomas to investigate the relation between GHRP-6 and TPA on membrane phosphatidylinositol (PI) turnover and GH secretion. The results showed that the working mechanisms of GHRP-6 and TPA are not identical, although they all can stimulate GH secretion in human pituitary somatotrophinomas. This indicates that PI-PKC signal transduction system may play a crucial role in the regulation of GH secretion.

Adenoma↗

Human meningiomas possess muscarinic acetylcholine receptors: stimulation of phosphatidylinositol turnover by carbachol.

The effect of carbachol, an acetylcholine receptor agonist, on rate of phosphatidylinositol (PI) turnover in cultured human meningioma cells was investigated. Exposure of meningioma cells for 2 h to carbachol (3.12-200 mumol/L) resulted in a dose-dependent stimulation of PI turnover to a maximum of 5.5-fold over basal controls. A time course study showed stimulation of IP3 formation after 30 s followed by increases in IP1 and IP2. The stimulatory effect of carbachol on PI turnover was completely abolished by the muscarinic receptor antagonist, atropine, but was unaltered by the nicotinic antagonist, hexamethonium. Reverse-transcription of meningioma-derived RNA into cDNA followed by amplification by the polymerase chain reaction using specific primers revealed presence of ml type muscarinic receptor mRNA. These results provide evidence that human meningioma cells possess muscarinic acetylcholine receptors the activation of which leads to PI hydrolysis.

Atropine↗