Biomedical subjects

Hua Zhou

Publications and source records attributed to Hua Zhou.

At least 37 records · Page 2Linked to original sources

PubMed2006

[Inhibitory effect of murine cytomegalovirus infection on neural stem cells' differentiation and its mechanisms].

OBJECTIVE: Cytomegalovirus (CMV) is the leading infectious cause of congenital anomalies of the central nervous system caused by intrauterine infection. However, the exact pathogenesis of these brain abnormalities has not been fully elucidated. It has been reported that periependymitis, periventricular necrosis and calcification are the most frequent findings in the brains of congenital CMV infection. Because a number of multipotential neural stem cells (NSCs) have been identified from ventricular zone, it is possible that NSCs in this area are primary targets for viral infection, which seems to be primarily responsible for the generation of the brain abnormalities. Therefore, the objective of the present study was to investigate the effect and mechanism of murine cytomegalovirus (MCMV) infection on neural stem cells' differentiation in vitro and its role in the mechanisms of brain abnormalities caused by congenital cytomegalovirus infection. METHODS: NSCs were prepared from fetal BALB/c mouse and were infected with recombinant MCMV RM461 inserted with a report gene LacZ at 1 multiplicity of infection (MOI = 1). The effect of MCMV infection on neural stem cells' differentiation was observed by detecting the ratio of nestin, GFAP and NSE positive cells with immunohistochemistry and flow cytometry on day 2 postinfection. The effects of MCMV infection on gene expression of Wnt-1 and neurogenin 1 (Ngn1) related to neural differentiation were detected by RT-PCR. RESULTS: NSCs isolated from embryonic mouse brains strongly expressed nestin, a specific marker of NSCs and had the capacity to differentiate into NF-200 and NSE positive neurons or GFAP positive astrocytes. At MOI = 1, the results of flow cytometry assay showed that nestin positive cells' proportion in the infection group [(62.2 +/- 1.8)%] was higher than that in the normal group [(37.2 +/- 2.4)%] (t = 4.62, P < 0.01). At the same time, the rates of GFAP and NSE positive cells' in the infection group were significantly lower than those in the normal group (P < 0.01). The scanning densities of Wnt-1 was 0.14 +/- 0.03 in the infection group while 0.32 +/- 0.04 in the control group (t = 7.21, P < 0.01). The scanning densities of Ngn1 were 0.09 +/- 0.01 and 0.21 +/- 0.02 in the two groups (t = 10.7, P < 0.01). CONCLUSIONS: These results suggest that MCMV infection could inhibit neuronal differentiation, which may be primary causes of disorders of brain development in congenital CMV infection. The decreased expression of Wnt-1 and Ngn1 may be involved in the inhibitory effect of murine cytomegalovirus infection on neural stem cells' differentiation, which may lead to a new strategy for preventing and treating brain abnormalities caused by CMV infection through regulating these two signal pathways.

Animals↗

PubMed2005

Urinary marker for oxidative stress in kidneys in cisplatin-induced acute renal failure in rats.

BACKGROUND: Establishment of non-invasive urinary biomarkers for the prediction of acute renal failure (ARF) is important. We evaluated whether urinary oxidative stress markers reflect intrarenal oxidative stress in cisplatin (CDDP)-induced ARF, and whether these markers can be used for the prediction of future ARF. METHODS: Urinary malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured up to day 14 post-CDDP (6 mg/kg) injection in rats. MDA and 8-OHdG expressions were examined in kidneys. RESULTS: CDDP induced an increase in serum creatinine (Scr), blood urea nitrogen (BUN), and tubular damage at day 5, increased urinary MDA excretion and MDA expression in kidneys at day 1 (but returned to basal values by day 3), increased urinary excretion of 8-OHdG at day 5 till day 14 (though the number of 8-OHdG-positive tubular cells increased at day 5 and then gradually decreased). Urinary MDA levels at day 1 correlated significantly with Scr (rho = 0.721, P < 0.01) and tubular damage score (rho = 0.840, P < 0.01) at day 5. CONCLUSION: Our findings demonstrated divergent changes of urinary oxidative stress markers in CDDP-induced ARF, and suggested that urinary MDA may be a useful marker for the prediction of the development of CDDP-induced ARF.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2005

Pharmacokinetic interaction of paeoniflorin and sinomenine: pharmacokinetic parameters and tissue distribution characteristics in rats and protein binding ability in vitro.

The root of Paeonia lactiflora and the stem of Sinomenium acutum are two herbs widely used in Chinese herbal medicine for the treatment of inflammatory and arthritic diseases. Studies on the interaction of the active constituents of these herbs, i.e., paeoniflorin and sinomenine, in pharmacokinetic parameters, tissues distribution, and protein binding ability could provide empirical data to support their clinical application. Following oral administration to rats, the pharmacokinetic alterations were compared. The results showed that the pharmacokinetic parameters (Cmax, Tmax, AUC, MRT, C(L), and Vd) of paeoniflorin were markedly enhanced when co-administrated with sinomenine. At 45 min after oral administration, the concentrations of paeoniflorin in the main internal organs were significantly increased when co-administrated with sinomenine. These phenomena were not ascribable to the alteration of the protein binding ability of paeoniflorin by sinomenine because obvious interactions of paeoniflorin and sinomenine in protein binding abilities in vitro to rat and rabbit plasma, human albumin, and alpha-1-acid-glycoprotein were not observed. However, with respect to the in vivo influence of paeoniflorin on sinomenine, the results showed that co-administration of paeoniflorin did not affect the pharmacokinetic parameters and tissue distribution of sinomenine.

Animals↗

PubMed2005

Expression of measles virus nucleocapsid protein in osteoclasts induces Paget's disease-like bone lesions in mice.

UNLABELLED: We targeted the MVNP gene to the OCL lineage in transgenic mice. These mice developed abnormal OCLs and bone lesions similar to those found in Paget's patients. These results show that persistent expression of MVNP in OCLs can induce pagetic-like bone lesions in vivo. INTRODUCTION: Paget's disease (PD) of bone is the second most common bone disease. Both genetic and viral factors have been implicated in its pathogenesis, but their exact roles in vivo are unclear. We previously reported that transfection of normal human osteoclast (OCL) precursors with the measles virus nucleocapsid (MVNP) or measles virus (MV) infection of bone marrow cells from transgenic mice expressing a MV receptor results in formation of pagetic-like OCLs. MATERIALS AND METHODS: Based on these in vitro studies, we determined if the MVNP gene from either an Edmonston-related strain of MV or a MVNP gene sequence derived from a patient with PD (P-MVNP), when targeted to cells in the OCL lineage of transgenic mice with the TRACP promoter (TRACP/MVNP mice), induced changes in bone similar to those found in PD. RESULTS: Bone marrow culture studies and histomorphometric analysis of bones from these mice showed that their OCLs displayed many of the features of pagetic OCLs and that they developed bone lesions that were similar to those in patients with PD. Furthermore, IL-6 seemed to be required for the development of the pagetic phenotype in OCLs from TRACP/MVNP mice. CONCLUSIONS: These results show that persistent expression of the MVNP gene in cells of the OCL lineage can induce pagetic-like bone lesions in vivo.

Animals↗

PubMed2005

A novel tetracycline labeling schedule for longitudinal evaluation of the short-term effects of anabolic therapy with a single iliac crest bone biopsy: early actions of teriparatide.

UNLABELLED: We describe a quadruple tetracycline labeling method that allows longitudinal assessment of short-term changes in bone formation in a single biopsy. We show that 1 month of hPTH(1-34) treatment extends the bone-forming surface, increases mineral apposition rate, and initiates modeling-based formation. INTRODUCTION: Iliac crest biopsy, with histomorphometric evaluation, provides important information about cellular activity in bone. However, to obtain longitudinal information, repeat biopsies must be performed. In this study, we show the capability to obtain short-term longitudinal information on bone formation in a single biopsy using a novel, quadruple labeling technique. MATERIALS AND METHODS: Two tetracycline labels were administered using a standard 3 days on, 12 days off, 3 days on format. Four weeks later, the tetracycline labeling was repeated using the same schedule but with a different tetracycline that can be distinguished from the first by its color under fluorescent light. Iliac crest biopsies were performed 1 week later and prepared undecalcified for histomorphometry. Indices of bone formation 1 month apart were measured and calculated using the two sets of labels. We used this method to investigate the early effects of teriparatide [hPTH(1-34)] treatment on bone formation. The results were compared with those from a group of control subjects who were quadruple-labeled, but did not receive hPTH(1-34). RESULTS: Treatment with hPTH(1-34) dramatically stimulated bone formation on cancellous and endocortical surfaces. This was achieved by both an increase in the linear rate of matrix apposition and extension of the bone-forming surface. New bone was deposited on previously quiescent surfaces (i.e., modeling-based formation), but a proportion of this could occur by encroachment from adjacent resorption cavities. CONCLUSIONS: A single transiliac crest bone biopsy, after sequential administration of two sets of tetracycline labels is a useful approach to study the short-term effects of anabolic agents on human bone. One month of hPTH(1-34) treatment extends the bone-forming surface, increases mineral apposition rate, and initiates modeling-based formation.

Anabolic Agents↗

PubMed2005

Saikosaponin-d inhibits T cell activation through the modulation of PKCtheta, JNK, and NF-kappaB transcription factor.

The effects of saikosaponin-d, a triterpene saponin derived from Bupleurum falcatum L. (Umbelliferae), on the signaling pathways of T cell activation were examined. The results showed that saikosaponin-d potently suppressed both early (CD69) and late (CD71) expressions of mouse T cells stimulated with Con A or PMA. It interfered with PKCtheta translocation from cytosol to membrane fraction and inhibited the phosphorylations of IkappaBalpha and JNK, but not ERK, in PMA-activated mouse T cells. Additionally, it inhibited PMA and ionomycin-stimulated IL-2 production in mouse T cells. In summary, these results indicate that the mechanism by which saikosaponin-d inhibits T cell activation would involve the suppression of CD69 and CD71 expressions and IL-2 production, and the modulation of PKC pathway through PKCtheta, JNK, and NF-kappaB transcription factor. This may herald a novel approach for further studies of saikosaponin-d as a candidate for use in the treatment of inflammatory and autoimmune diseases.

Animals↗

PubMed2005

Simultaneous determination of six Aconitum alkaloids in proprietary Chinese medicines by high-performance liquid chromatography.

By optimizing the extraction, separation and analytical conditions, a reliable and accurate high-performance liquid chromatography (HPLC) method coupled with photodiode array detector (DAD) was developed for simultaneous quantitative determination of six Aconitum alkaloids, i.e., aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine, in Chinese medicinal herbs, aconite roots, and 12 proprietary Chinese medicines containing processed aconite roots. The separation of these Aconitum alkaloids was achieved on an ODS column with gradient elution using solvents of acetonitrile and ammonium bicarbonate buffer (pH 10.0+/-0.2). Intra-assay and inter-assay precision of the analytes were less than 2.97%, and the average recovery rates obtained were in the range of 90-103% for all with RSDs below 3.28%. Good linear relationships were showed with correlation coefficients for the analytes exceeded 0.999. Quantitative analysis of the six Aconitum alkaloids in the unprocessed and processed aconite roots and in twelve proprietary Chinese medicines containing processed aconite roots showed that the contents of the alkaloids varied significantly. This method and quantitation results can provide a scientific and technical platform to the products manufacturers for setting up a quality control standard as well as to the public for quality and safety assurance of the proprietary Chinese medicines and other herbal preparations containing aconite roots.

Aconitum↗

PubMed2005

Acute gamma-secretase inhibition improves contextual fear conditioning in the Tg2576 mouse model of Alzheimer's disease.

Transgenic mice (Tg2576) overexpressing the Swedish mutation of the human amyloid precursor protein display biochemical, pathological, and behavioral markers consistent with many aspects of Alzheimer's disease, including impaired hippocampal function. Impaired, hippocampal-dependent, contextual fear conditioning (CFC) is observed in mice as young as 20 weeks of age. This impairment can be attenuated after treatment before training with the phosphodiesterase-4 inhibitor rolipram (0.1 mg/kg, i.p.). A rolipram-associated improvement is also observed in the littermate controls, suggesting that the effect of rolipram is independent of beta-amyloid. Acute treatment before training (but not after training or before testing) with the gamma-secretase inhibitor (GSI) N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine-t-butylester (DAPT), at a dose that reduces brain concentrations of beta-amyloid (100 mg/kg), attenuates the impairment in 20- to 65-week-old Tg2576 mice. Importantly, DAPT had no effect on performance of control littermates. These data are supportive of a role of beta-amyloid in the impairment of CFC in Tg2576 mice. Furthermore, they suggest that acute treatment with GSI may provide improved cognitive functioning as well as disease-modifying effects in Alzheimer's disease.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2005

Suppressive effects of QFGJS, a preparation from an anti-arthritic herbal formula, on rat experimental adjuvant-induced arthritis.

To analyze the anti-arthritic effects of QFGJS (a pharmaceutical preparation from herbs) on rheumatoid arthritis, adjuvant-induced arthritis (AIA) was established in male SD rats, and two administration protocols, i.e., oral treatment with different doses of QFGJS on the day of arthritis induction or on the day when visible clinical signs of arthritis occurred, were initiated and continued until day 30. Treatments with QFGJS using both administration protocols significantly suppressed the incidence and severity of arthritis in a dose-dependent manner, showing dramatic reduction of paw swelling and ESR throughout the disease progression of AIA. Radiological and histopathological examinations showed markedly decreased tissue and bone destruction of ankle joints in the QFGJS-treated rats. The serum levels of TNF-alpha, IL-1beta, and IL-6 were significantly decreased in the QFGJS-treated rats. QFGJS demonstrates pronounced anti-arthritic effects on AIA, indicating that this herbal preparation would be a potent candidate as a novel botanical drug for further investigation.

Animals↗

PubMed2005

The effects of sinomenine on intestinal absorption of paeoniflorin by the everted rat gut sac model.

Paeoniflorin and sinomenine, derived from the root of Paeonia lactiflora Pall. (family Ranunculaceae) and the stem of Sinomenium acutum Rehder & Wilson (family Menispermaceae), respectively, have been, and are currently, widely used for treatment of rheumatic and arthritic diseases in China and Japan. Our previous studies demonstrated that sinomenine could significantly improve the bioavailability of paeoniflorin in rats, but the underlying mechanisms remain unknown. The present study aims to investigate the intestinal kinetic absorptive characteristics of paeoniflorin as well as the absorptive behavior influenced by co-administration of sinomenine using an in vitro everted rat gut sac model. The results showed a good linear correlation between the paeoniflorin absorption in sac contents and the incubation time from 0 to 90 min. However, the concentration dependence showed that a non-linear correlation exists between the paeoniflorin absorption and its concentrations from 10 to 160 microM, and the absorption was saturated at about 80 microM of the drug. Sinomenine at 16 and 136 microM concentrations could significantly enhance the absorption of paeoniflorin (20 microM) by 1.5- and 2.5-fold, respectively. Moreover, two well-known P-glycoprotein inhibitors, verapamil and quinidine, could significantly elevate the absorption of paeoniflorin by 2.1- and 1.5-fold, respectively. Furthermore, sinomenine in a pattern, which influenced paeoniflorin's absorption, manifested as similar to that of P-glycoprotein inhibitors. In conclusion, sinomenine significantly enhance the intestinal absorption of paeoniflorin, subsequently improve the bioavailability of paeoniflorin. The mechanism underlying the improvement of paeoniflorin's bioavailability was proposed that sinomenine could decrease the efflux transport of paeoniflorin by P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Autologous skeletal myoblast transplantation improved hemodynamics and left ventricular function in chronic heart failure dogs.

BACKGROUND: Previous studies have suggested that autologous skeletal myoblast transplantation (ASMT) improves left ventricular (LV) function in small animals after myocardial infarction. We tested the effects of ASMT on hemodynamics, LV function and remodeling in coronary microembolization-induced chronic heart failure (CHF) in conscious dogs. METHODS: Nineteen dogs were continuously instrumented with LV pressure sensors and mid-myocardial sonomicrometry crystals for dP/dt(max) and LV volume determination. Each dog underwent baseline assessment in a conscious state. CHF (20% to 30% reduction in dP/dt(max) and LV end-diastolic pressure >16 mm Hg) was created by daily coronary microembolizations via a continuously implanted coronary catheter. Skeletal muscle biopsy was performed and myoblasts were isolated and expanded. Then 2.7 x 10(8) to 8.3 x 10(8) myoblasts were injected into the infarcted region of 11 dogs after establishment of CHF. Saline injection (sham) was performed in 8 control dogs. Animals were evaluated every 2 weeks for up to 10 weeks. Global ejection fraction was determined by echocardiography. The end-systolic pressure-end-systolic volume relationship (ESPVR) was analyzed by the Sonomicrometic system. RESULTS: Compared with saline injection, ASMT significantly increased dP/dt(max) (105 +/- 9% vs 97 +/- 7%, values were expressed as percentage change from baseline CHF, p = 0.013) and ejection fraction (46 +/- 3% vs 40 +/- 2%, p = 0.034) at 10 weeks after myoblast transplantation. There was a significant leftward and upward shift of the ESPVR back toward normal at 10 weeks after myoblast transplantation (p = 0.034). Three animals labeled with BrdU myoblasts showed no histologic evidence of viable engraftment. CONCLUSIONS: ASMT provided mild improvements in hemodynamics and LV function and reduced LV remodeling in conscious dogs with CHF.

Animals↗

PubMed2005

The pharmacokinetics and tissue distribution of sinomenine in rats and its protein binding ability in vitro.

Sinomenine, an alkaloid derived from the Chinese medical plant Sinomenium acutum, was studied with regard to its pharmacokinetics and tissue distribution in rats, and to its protein binding ability in the plasma of rats and rabbits and in the solutions of albumin and alpha-1-acid-glycoprotein. An HPLC analytical method was developed for determining sinomenine. The results demonstrated that oral administration with a single dosage at a rate of 90 mg sinomenine/kg in rats achieved about 80% bioavailability, while most of the other pharmacokinetic parameters were similar to the data from the animals treated intravenously. This indicates that oral administration of sinomenine would be appropriate in clinics. In rats, at 45 min after oral dosage, the drug was found to distribute widely in the internal organs, with tissue concentrations (from highest to lowest) in the order of kidneys, liver, lungs, spleen and heart, brain and testicles. At 90 min after dosing, the tissue concentrations in the organs were markedly decreased. The liver and kidneys manifested as the dominant organs with high tissue concentrations that might be responsible for metabolism and elimination of sinomenine. Examination of the protein binding ability showed that sinomenine with 4 microg/ml concentration in the plasma of rats and rabbits or in the albumin solution achieved a protein binding rate of more than 60%, while in the solution of alpha-1-acid-glycoprotein the rate was only about 33%. This result suggests that sinomenine might have much more potent binding ability with albumin than with alpha-1-acid-glycoprotein, resulting from its acidic property.

Administration, Oral↗

PubMed2005

[Experimental study on preparation of decellularized artery vascular graft matrix and explantation of carotid artery allografts].

OBJECTIVE: To set up a new process to access the preparation of decellularized artery grafts. And to evaluate the feasibility of decellularized artery allografts was evaluated. METHODS: This study compared the effects of four extraction chemicals [1% t-octyl-phenoxypolyethoxyethanol (Triton X-100), 1% tri (n-butyl) phosphate (TnBP), and 1% sodium dodecyl sulfate (SDS) and trypsin (0.125, 0.25%) on thoracic artery vascular for 24 h (except trypsin for 2 h). At the base of it, a four-step process, including hypotonic, hypertonic solutions and combining with 1% Triton X-100 and 1% SDS detergents, were performed in rabbit thoracic artery vascular. Histological examination, tensile tests and expanding-burst tests were done on the samples. The decellularized carotid artery allografts were transplanted in other rabbits. RESULTS: Treatment with 1% SDS or 1% Triton X-100 for 24 h could remove most cells with retention of near normal structure. A four-step process could remove all cells with the extracellular matrix well conserved. The pulling mechanical properties and burst pressure of decellularized carotid artery were similar to the control. The decellularized carotid artery allografts (diameter of 2 mm) were patent at explanting up to 2 months. CONCLUSIONS: The acellular artery vascular graft matrix is well prepared with four-step process including detergents, such as TritonX-100, SDS without compromising the graft structure or mechanical properties significantly. The carotid artery allografts (diameter of 2 mm) decellularized by the process are patent at explanting up to 2 months.

Animals↗

PubMed2005

Influence of co-administrated sinomenine on pharmacokinetic fate of paeoniflorin in unrestrained conscious rats.

Paeonia lactiflora Pall. (Ranunculaceae) root and Sinomenium acutum Rehder and Wilson (Menispermaceae) stem are two herbs widely used in Chinese medicine to treat rheumatoid arthritis. While, in theory, either herb could be used alone, in practice, Chinese medicine practitioners prescribe them together. Studies on pharmacokinetic interaction between the active constituents of these two herbs (paeoniflorin and sinomenine, respectively) provide empirical evidence to support their clinical practice. A single dose of paeoniflorin (150 mg/kg) alone and with sinomenine hydrochloride (90 mg/kg) was administered by gastric gavage to unrestrained conscious male Sprague-Dawley rats (n=5 or 6, 240-270 [corrected] g). Blood samples were collected periodically via a jugular vein before and after dosing from 10 min to 12 h. A high-performance liquid chromatographic (HPLC) assay was developed to determine the plasma concentrations of paeoniflorin. Non-compartmental pharmacokinetic profiles were constructed by using the software PK Solutions 2.0. The pharmacokinetic parameters were compared using unpaired Student t-test. After co-administration of sinomenine, the peak plasma concentration of paeoniflorin was elevated (P<0.01), the peak time was delayed (P<0.01), the AUC(0-t) was increased (P<0.001), the mean residence time (MRT) was prolonged (P<0.01), the C(L) was decreased (P<0.01) and the V(d) was reduced (P<0.05). These results indicate that sinomenine hydrochloride at 90 mg/kg significantly improved the bioavailability of paeoniflorin in rats.

Animals↗

PubMed2005

CD147 is a regulatory subunit of the gamma-secretase complex in Alzheimer's disease amyloid beta-peptide production.

gamma-Secretase is a membrane protein complex that cleaves the beta-amyloid precursor protein (APP) within the transmembrane region, after prior processing by beta-secretase, producing amyloid beta-peptides Abeta(40) and Abeta(42). Errant production of Abeta-peptides that substantially increases Abeta(42) production has been associated with the formation of amyloid plaques in Alzheimer's disease patients. Biophysical and genetic studies indicate that presenilin-1, which contains the proteolytic active site, and three other membrane proteins [nicastrin, anterior pharynx defective-1 (APH-1), and presenilin enhancer-2 (PEN-2)] are required to form the core of the active gamma-secretase complex. Here, we report the purification of the native gamma-secretase complexes from HeLa cell membranes and the identification of an additional gamma-secretase complex subunit, CD147, a transmembrane glycoprotein with two Ig-like domains. The presence of this subunit as an integral part of the complex itself was confirmed through coimmunoprecipitation studies of the purified protein from HeLa cells and of solubilized complexes from other cell lines such as neural cell HCN-1A and HEK293. Depletion of CD147 by RNA interference was found to increase the production of Abeta peptides without changing the expression level of the other gamma-secretase components or APP substrates whereas CD147 overexpression had no statistically significant effect on Abeta-peptide production, other gamma-secretase components or APP substrates, indicating that the presence of the CD147 subunit within the gamma-secretase complex down-modulates the production of Abeta-peptides.

Alzheimer Disease↗

PubMed2005

Molecular-modeling based design, synthesis, and activity of substituted piperidines as gamma-secretase inhibitors.

Alzheimer's disease (AD) is a debilitating disease widely thought to be associated with the accumulation of beta amyloid (Abeta) in the brain. Inhibition of gamma-secretase, one of the enzymes responsible for Abeta production, may be a useful strategy for the treatment of AD. Described below is a series of gamma-secretase inhibitors designed from a scaffold identified by a ROCS [J. Comput. Chem.1996, 17, 1653] search of the corporate database.

Alzheimer Disease↗

PubMed2005

Low bone formation in premenopausal women with idiopathic osteoporosis.

Most young people with osteoporosis have an identifiable cause. Others have an idiopathic form for which no etiology can be found. We have reported that men with idiopathic osteoporosis (IOP) have histomorphometric evidence of decreased bone formation and osteoblast dysfunction. The pathogenesis of IOP in young women remains unclear. Our aim was to characterize the histomorphometry of IOP in healthy premenopausal women. We compared iliac crest bone biopsies from nine women with IOP to 18 healthy, age-, sex-, and race-matched controls. Compared with controls, differences in bone remodeling were identified, particularly in cancellous bone. Although cancellous bone volume did not differ, there was a trend toward lower trabecular number and increased separation in women with IOP. In cancellous bone, there was no increase in osteoid width or perimeter, but IOP patients had lower bone formation parameters, including a 10% reduction in wall width (P < 0.01), an 18% reduction in mineral apposition rate (P < 0.01), and a 42% reduction in mineralized perimeter (P < or = 0.02). Additionally, the bone formation rate was 52% lower (0.026 +/- 0.004 vs. 0.054 +/- 0.01 microm/microm(2).d; P < 0.01), and a trend toward decreased activation frequency was observed in IOP patients. Conversely, bone resorption was altered in IOP patients, reflected by a longer resorption period (134 +/- 35 vs. 38 +/- 6 d; P < or = 0.02) and increased eroded perimeter (5.5 +/- 0.7 vs. 4.1 +/- 0.4%; P = 0.05). Wall width and mineralized perimeter were similarly lower in endocortical bone. Resorption period and eroded perimeter were higher in intracortical bone. Women with IOP have uncoupling of resorption and formation and, like men with IOP, osteoblast dysfunction.

Adult↗

PubMed2005

Tumor cell invasion and survival in head and neck cancer.

Squamous cell carcinoma (SCC) is the primary tumor type in head and neck cancer. Typically, these tumor cells show persistent invasion that frequently leads to local recurrence and distant lymphatic metastasis. The process of invasion involves concurrent infiltration and destruction of adjacent tissues. As with normal mucosal epithelium, SCC cells express receptors that mediate cell-extracellular matrix (ECM) adhesion (integrins) and cell-cell adhesion (cadherins). Both receptor families represent important signaling devices that are capable of promoting survival and proliferation. Recent results indicate that integrins and cadherins cooperate to regulate invasive behavior. During SCC invasion, cells actively migrate through the surrounding ECM with the simultaneous remodeling of their intercellular adhesions. During invasion, integrin receptor engagement with specific ECM ligands along with concurrent remodeling of cadherin adhesions induces changes in the cytoskeleton though modulation of the activities of Rho family members. Tumor development and progression of SCC proceeds with the generation of variant cells with potential alterations in expression of adhesion receptors, and their associated signaling pathways lead to a highly invasive and metastatic phenotype. Understanding the molecular events that define this subset of invasive cells will facilitate the development of new treatment strategies.

Animals↗