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Biomedical subjects

Xin Huang

Publications and source records attributed to Xin Huang.

At least 73 records · Page 4Linked to original sources

Deletion 6q is not a characteristic marker of nodal lymphoplasmacytic lymphoma.

Lymphoplasmacytic lymphoma (LPL) is a small B-cell neoplasm with plasmacytic differentiation that does not fulfill the criteria for any other type of B-cell leukemia or lymphoma. In many cases, LPL is associated with Waldenström macroglobulinemia (WM), although WM may also be associated with other types of lymphoma. Recent studies have demonstrated that del(6q) is the most common structural abnormality in patients with bone marrow-based LPL. It is unknown whether del(6q) might also be associated with nodal LPL. We, therefore, examined 10 well-characterized LPL involving lymph nodes or other extramedullary tissues for del(6q) using paraffin section interphase fluorescence in situ hybridization (FISH). Dual-color FISH was performed using a chromosome 6 centromere probe (CEP6) and a probe for 6q21 (RP11-91C23). The latter probe has previously been reported as deleted in up to 63% of cases of bone marrow-based LPL. In contrast, no nuclei containing a del(6q) pattern were identified in any case of extramedullary LPL examined in this study, and 89-98.5% of nuclei contained a normal signal pattern. These results indicate that del(6q) is at least uncommon in nodal LPL, and cannot be employed as a diagnostic marker to identify this type of lymphoma. Furthermore, these findings suggest that nodal LPL and bone marrow-based cases of LPL may be associated with different cytogenetic findings.

Biomarkers, Tumor↗

A soluble tissue factor-annexin V chimeric protein has both procoagulant and anticoagulant properties.

Tissue factor (TF) initiates blood coagulation, but its expression in the vascular space requires a finite period of time. We hypothesized that targeting exogenous tissue factor to sites of vascular injury could lead to accelerated hemostasis. Since phosphatidylserine (PS) is exposed on activated cells at sites of vascular injury, we cloned the cDNA for a chimeric protein consisting of the extracellular domain of TF (called soluble TF or sTF) and annexin V, a human PS-binding protein. Both the sTF and annexin V domains had ligand-binding activities consistent with their native counterparts, and the chimera accelerated factor X activation by factor VIIa. The chimera exhibited biphasic effects upon blood coagulation. At low concentrations it accelerated blood coagulation, while at higher concentrations it acted as an anticoagulant. The chimera accelerated coagulation in the presence of either unfractionated or low-molecular-weight heparins more potently than factor VIIa and shortened the bleeding time of mice treated with enoxaparin. The sTF-annexin V chimera is a targeted procoagulant protein that may be useful in accelerating thrombin generation where PS is exposed to the vasculature, such as may occur at sites of vascular injury or within the vasculature of tumors.

Animals↗

Stable gene transfer and expression in human primary T cells by the Sleeping Beauty transposon system.

The Sleeping Beauty (SB) transposon system is a nonviral DNA delivery system in which a transposase directs integration of an SB transposon into TA-dinucleotide sites in the genome. To determine whether the SB transposon system can mediate stable gene expression in human T cells, primary peripheral blood lymphocytes (PBLs) were nucleofected with SB vectors carrying a DsRed reporter gene. Plasmids containing the SB transposase on the same molecule as (cis) or on a molecule separate from (trans) the SB transposon mediated long-term and stable reporter gene expression in human primary T cells. Sequencing of transposon:chromosome junctions confirmed that stable gene expression was due to SB-mediated transposition. In other studies, PBLs were successfully transfected using the SB transposon system and shown to stably express a fusion protein consisting of (1) a surface receptor useful for positive T-cell selection and (2) a "suicide" gene useful for elimination of transfected T cells after chemotherapy. This study is the first report demonstrating that the SB transposon system can mediate stable gene transfer in human primary PBLs, which may be advantageous for T-cell-based gene therapies.

Animals↗

Pharmacologic and toxicologic evaluation of C. novyi-NT spores.

Clostridium novyi-NT (C. novyi-NT) spores have been shown to be potent therapeutic agents in experimental tumors of mice and rabbits. In the present study, pharmacologic and toxicologic studies were performed to better understand the factors influencing the efficacy and toxicity of this form of therapy. We found that spores were rapidly cleared from the circulation by the reticuloendothelial system. Even after large doses were administered, no clinical toxicity was observed in healthy mice or rabbits. The spores were also not toxic in mice harboring poorly vascularized non-neoplastic lesions, including myocardial infarcts. In tumor-bearing mice, toxicity appeared related to tumor size and spore dose, as expected with any bacterial infection. However, there was no laboratory or histopathologic evidence of sepsis, and the toxicity could be effectively controlled by simple hydration.

Animals↗

Serum proteomics study of the squamous cell carcinoma antigen 1 in tongue cancer.

The identification of serum biomarkers as a means of the early diagnosis and finding possible therapeutic targets in cancers is of increasing interest. In the present study, cells of human tongue cancer cell line Tca8113 were subcutaneously inoculated into nude mice, while control nude mice were injected with phosphate-buffered saline. Two weeks after injection, serum from mice was collected for proteomic analysis using two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). Comparing the serum 2-DE maps from the tumor-bearing mice with those produced from control mice, we found that squamous cell carcinoma antigen 1 was over-expressed only in tumor-bearing mice. Squamous cell carcinoma antigen 1 was also up-regulated in clinical tongue cancer patients by RT-PCR and Western-blotting. These results indicate that squamous cell carcinoma antigen 1 may be of great potential as the biomarker of tongue cancer and as the potential therapeutic target for gene therapy.

Animals↗

Hepatocyte growth factor promotes cancer cell migration and angiogenic factors expression: a prognostic marker of human esophageal squamous cell carcinomas.

PURPOSE: Hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, c-Met, play important roles in tumor development and progression. In this study, we measured the serum HGF levels in patients with esophageal squamous cell carcinoma (ESCC) to evaluate its relationships with clinicopathologic features and the role of HGF in ESCC. EXPERIMENTAL DESIGN: One hundred and forty-nine patients with ESCC were studied. Pretherapy serum was collected and ELISA was used to detect the concentrations of HGF, vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8). The function of HGF was shown by invasion chamber assay. RESULTS: Pretherapy serum HGF was found to be significantly higher in patients with ESCC than in control subjects. The levels of HGF correlated significantly with advanced tumor metastasis stage and survival. Multivariate analyses showed that serum HGF level in cell migration was an independent prognostic factor. Increased HGF serum levels correlated positively with serum levels of VEGF and IL-8. Our results also showed that HGF was overexpressed in ESCC tissues and cell lines. In vitro study showed that HGF could stimulate ESCC cell to express VEGF and IL-8 and markedly enhance invasion and migration of ESCC cells. Furthermore, HGF-induced IL-8 and VEGF expression was dependent on extracellular signal-regulated kinase signaling pathways. The inhibition of extracellular signal-regulated kinase activation reduced HGF-mediated IL-8 and VEGF expression. CONCLUSIONS: Our results suggest that serum HGF may be a useful biomarker of tumor progression and a valuable independent prognostic factor in patients with ESCC. HGF may be involved in the progression of ESCC as an autocrine/paracrine factor via enhancing angiogenesis and tumor cell invasion and migration.

Aged↗

Background changes delay information represented in macaque V1 neurons.

In natural behavioral situations, saccadic eye movements not only introduce new stimuli into V1 receptive fields, they also cause changes in the background. We recorded in awake macaque V1 using a fixation paradigm and compared evoked activity to small stimuli when the background was either static or changing as with a saccade. When a stimulus was shown on a static background, as in most previous experiments, the initial response was orientation selective and contrast was inversely correlated with response latency. When a stimulus was introduced with a background change, V1 neurons showed a qualitatively different temporal response pattern in which information about stimulus orientation and contrast was delayed. The delay in the representation of visual information was found with three different types of background change-luminance increment, luminance decrement, and a pattern change with fixed mean luminance. We also found that with a background change, V1 off responses were suppressed and had a shorter time course compared with the static-background situation. Our results suggest that the distribution of temporal changes across the visual field plays a fundamental role in determining V1 responses. In the static-background condition, temporal change in the visual input occurs only in a small portion of the visual field. In the changing-background condition, and presumably in natural vision, temporal changes are widely distributed. Thus a delayed representation of visual information may be more representative of natural visual situations.

Action Potentials↗

Background changes delay the perceptual availability of form information.

In natural visual situations, unlike most psychophysical experiments, when a new stimulus appears in a portion of the visual field, the surrounding background changes simultaneously. In recordings from macaque V1, we found that a visual stimulus presented simultaneously with a background change evokes a response that is qualitatively different from the response to the same stimulus flashed on a static background. With the changing background, information about stimulus orientation and contrast is significantly delayed compared with the static-background situation. Our physiological results make several predictions that we test in the present paper with human psychophysical experiments. In a backward masking paradigm, a bar stimulus was either flashed onto a static background or presented simultaneously with a change in background luminance or pattern. Subjects discriminated bar orientation or detected that the scene changed before the mask. To achieve an equivalent contrast threshold for orientation discrimination, a longer stimulus-mask onset asynchrony (SOA) was needed in the changing than in the static-background condition; to match the orientation discrimination performance in the static and changing-background conditions at a fixed SOA, a higher bar contrast was needed when the background changed. Moreover, in the changing-background condition, a longer SOA was needed to discriminate bar orientation than to detect the scene change. These results suggest that orientation information is available more slowly when the background changes; orientation information is available earlier as stimulus contrast increases. The psychophysical findings are consistent with our physiological predictions. Compared with the common technique of flashing stimuli onto a static background, the changing-background paradigm may be more similar to natural vision in which saccades bring new stimuli and backgrounds into the visual field.

Contrast Sensitivity↗

Bacterial redox protein azurin induce apoptosis in human osteosarcoma U2OS cells.

As a low molecular weight redox protein elaborated from the pathogenic bacteria Pseudomonas aeruginosa, azurin is one of representative bacterial products applied in the treatment of tumour. We found that the growth of U2OS cells was significantly inhibited by azurin in a dose-dependent manner with the IC(50) value of 114.54+/-7.65 mgl(-1). But the growth of MG63 cells or L02 cells was almost not inhibited by azurin (P<0.05). Moreover, when treated with azurin, U2OS cells showed typical apoptotic morphological features observed by fluorescent microscopy (AO and Hoechst 33258) and transmission electron microscopy. Typical DNA "ladder" bands were also observed. The apoptosis rate was 35.8% tested by fluorescence-activated cell sorter (Annexin-V-FITC(+)/PI(-)) and the cell-cycle arrested in G(1) phase. But no apoptotic features were observed in control cells. The down-regulation of Bcl-2 (an inhibitor of apoptosis) were detected in U2OS cells when azurin was added for 24h. In contrast, the level of Bax and caspase-3 were significantly up-regulated. So we concluded that azurin could selectively induce apoptosis of human osteosarcoma U2OS cells and the induction of apoptosis by azurin was closely associated with down-regulation of Bcl-2, up-regulation of Bax and activation of caspase-3.

Apoptosis↗

Electronic and structural evolution and chemical bonding in ditungsten oxide clusters: W2O(n)- and W2O(n) (n = 1-6).

We report a systematic and comprehensive investigation of the electronic structures and chemical bonding in a series of ditungsten oxide clusters, W2O(n)- and W2O(n) (n = 1-6), using anion photoelectron spectroscopy and density functional theory (DFT) calculations. Well-resolved photoelectron spectra were obtained at several photon energies (2.331, 3.496, 4.661, 6.424, and 7.866 eV), and W 5d-based spectral features were clearly observed and distinguished from O 2p-based features. More complicated spectral features were observed for the oxygen-deficient clusters because of the W 5d electrons. With increasing oxygen content in W2O(n)-, the photoelectron spectra were observed to shift gradually to higher binding energies, accompanied by a decreasing number of W 5d-derived features. A behavior of sequential oxidation as a result of charge transfers from W to O was clearly observed. A large energy gap (2.8 eV) was observed in the spectrum of W2O6-, indicating the high electronic stability of the stoichiometric W2O6 molecule. Extensive DFT calculations were carried out to search for the most stable structures of both the anion and neutral clusters. Time-dependent DFT method was used to compute the vertical detachment energies and compare to the experimental data. Molecular orbitals were used to analyze the chemical bonding in the ditungsten oxide clusters and to elucidate their electronic and structural evolution.

Journal Article↗

Prediction of lymph node metastasis by analysis of gene expression profiles in primary lung adenocarcinomas.

PURPOSE: Lymph node status is a strong predictor of outcome for lung cancer patients. Recently, several reports have hinted that gene expression profiles of primary tumor may be able to predict node status. The goals of this study were to determine if microarray data could be used to accurately classify patients with regard to pathologic lymph node status, and to determine if this analysis could identify patients at risk for occult disease and worse survival. EXPERIMENTAL DESIGN: Two previously published lung adenocarcinoma microarray data sets were reanalyzed. Patients were separated into two groups based on pathologic lymph node positive (pN+) or negative (pN0) status, and prediction analysis of microarray (PAM) was used for training and validation to classify nodal status. Overall survival analysis was performed based on PAM classifications. RESULTS: In the training phase, a 318-gene set gave classification accuracy of 88.4% when compared with pathology. Survival was significantly worse in PAM-positive compared with PAM-negative patients overall (P < 0.0001) and also when confined to pN0 patients only (P = 0.0037). In the validation set, classification accuracy was again 94.1% in the pN+ patients but only 21.2% in the pN0 patients. However, among the pN0 patients, recurrence rates and overall survival were significantly worse in the PAM-positive compared with PAM-negative patients (P = 0.0258 and 0.0507). CONCLUSIONS: Analysis of gene expression profiles from primary tumor may predict lymph node status but frequently misclassifies pN0 patients as node positive. Recurrence rates and overall survival are worse in these "misclassified" patients, implying that they may in fact have occult disease spread.

Adenocarcinoma↗

Somatic mutation and gain of copy number of PIK3CA in human breast cancer.

INTRODUCTION: Phosphatidylinositol 3-kinases (PI3Ks) are a group of lipid kinases that regulate signaling pathways involved in cell proliferation, adhesion, survival, and motility. Even though PIK3CA amplification and somatic mutation have been reported previously in various kinds of human cancers, the genetic change in PIK3CA in human breast cancer has not been clearly identified. METHODS: Fifteen breast cancer cell lines and 92 primary breast tumors (33 with matched normal tissue) were used to check somatic mutation and gene copy number of PIK3CA. For the somatic mutation study, we specifically checked exons 1, 9, and 20, which have been reported to be hot spots in colon cancer. For the analysis of the gene copy number, we used quantitative real-time PCR and fluorescence in situ hybridization. We also treated several breast cancer cells with the PIK3CA inhibitor LY294002 and compared the apoptosis status in cells with and without PIK3CA mutation. RESULTS: We identified a 20.6% (19 of 92) and 33.3% (5 of 15) PIK3CA somatic mutation frequency in primary breast tumors and cell lines, respectively. We also found that 8.7% (8 of 92) of the tumors harbored a gain of PIK3CA gene copy number. Only four cases in this study contained both an increase in the gene copy number and a somatic mutation. In addition, mutation of PIK3CA correlated with the status of Akt phosphorylation in some breast cancer cells and inhibition of PIK3CA-induced increased apoptosis in breast cancer cells with PIK3CA mutation. CONCLUSION: Somatic mutation rather than a gain of gene copy number of PIK3CA is the frequent genetic alteration that contributes to human breast cancer progression. The frequent and clustered mutations within PIK3CA make it an attractive molecular marker for early detection and a promising therapeutic target in breast cancer.

Apoptosis↗

Uncommon mutation, but common amplifications, of the PIK3CA gene in thyroid tumors.

CONTEXT: As in many other human cancers, overactivation of the phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathway occurs frequently in thyroid cancer, but the mechanism is not completely clear. OBJECTIVE: Because activating mutations and genomic amplification of the PIK3CA gene, which encodes the p110a catalytic subunit of PI3K, are common in many cancers, we sought to investigate this phenomenon in thyroid tumors. DESIGN: To search for PIK3CA mutations, we isolated genomic DNA from primary thyroid tumors of various types and performed direct sequencing of the exons of PIK3CA gene that carry the most common mutations in other cancers. We used real-time quantitative PCR to investigate genomic amplification of the PIK3CA gene. RESULTS: We found no PIK3CA gene mutations in 37 benign thyroid adenomas, 52 papillary thyroid cancers, 25 follicular thyroid cancers, 13 anaplastic thyroid cancers, 13 medullary thyroid cancers, and seven thyroid tumor cell lines. We found a C3075T single-nucleotide polymorphism in exon 20 of this gene in two cases. With a copy number of 4 or more defined as amplification, we found PIK3CA gene amplification in four of 34 (12%) benign thyroid adenomas, three of 59 (5%) papillary thyroid cancer, five of 21 (24%) follicular thyroid cancer, none of 14 (0%) medullary thyroid cancer, and five of seven (71%) thyroid tumor cell lines. The PIK3CA gene amplification and consequent Akt activation were confirmed by fluorescence in situ hybridization and Western blotting studies using cell lines, respectively. CONCLUSION: These data suggest that mutation of the PIK3CA gene is not common, but its amplification is relatively common and may be a novel mechanism in activating the PI3K/Akt pathway in some thyroid tumors.

Class I Phosphatidylinositol 3-Kinases↗

Syndecan-1 and E-cadherin expression in differentiated type of early gastric cancer.

AIM: To elucidate the role and alterations of syndecan-1 and E-cadherin expression in different cellular phenotypes of differentiated-type gastric cancers (DGCs). METHODS: A total of 120 DGCs at an early stage, and their adjacent mucosa, were studied both by immunohistochemistry. Syndecan-1 and E-cadherin were assessed by immunohistochemical staining with anti-syndecan-1 and anti-E-cadherin antibodies, respectively. Based on immunohistochemistry, DGCs and their surrounding mucosa were divided into four types: gastric type (G-type), ordinary type (O-type), complete-intestinal type (CI-type), and null type (N-type). RESULTS: Syndecan-1 expression was significantly lower in G-type cancers (29.4%) than in O-type (79.6%) and CI-type cancers (90%) (P<0.05, respectively), but E-cadherin did not show this result. In addition, syndecan-1 expression was significantly reduced in DGCs comprised partly of poorly differentiated adenocarcinoma or signet-ring cell carcinoma, compared to DGCs demonstrating papillary and/or tubular adenocarcinoma (P<0.05). G-type intestinal metaplasia (IM) surrounding the tumors was observed in 23.8% of G-type, 4.9% of O-type, and 6.7% of CI-type cancers (P<0.05; G-type vs O-type). Reduction of syndecan-1 expression was significant in G-type IM (25%) compared to non-G-type IM (75%; P<0.05). CONCLUSION: Loss of syndecan-1 plays a role in the growth of G-type cancers of DGCs at an early stage, and the reduction of syndecan-1 expression in IM surrounding the tumors may influence the growth of G-type cancer.

Adenocarcinoma↗

Supramolecular chirality of the hydrogen-bonded complex Langmuir-Blodgett film of achiral barbituric acid and melamine.

Complex monolayers of barbituric acid and melamine were formed by spreading a chloroform solution of amphiphilic barbituric acid on the subphase of melamine solution. It was confirmed that the complex monolayer was formed through in situ complementary hydrogen bonding at the air-water interface. It was interesting to find that the complex LB films showed supramolecular chirality although both of the molecules were achiral, as verified by the circular dichroism spectral measurements. It was suggested that the pi-pi stacking of the neighboring barbituric acid and melamine group in a helical sense resulted in the chirality of the molecular assemblies. Due to the directionality of the hydrogen bonding, the BA-M film could form regular aligned nanofibers on the AFM images. Increasing the subphase temperature will lead to the decrease of CD intensity and the change of the morphologies. We suggested that the strength of the hydrogen bonding resulted in the difference.

Barbiturates↗

Diverse CD8+ T-cell responses to renal cell carcinoma antigens in patients treated with an autologous granulocyte-macrophage colony-stimulating factor gene-transduced renal tumor cell vaccine.

A phase I clinical trial with granulocyte-macrophage colony-stimulating factor tumor cell vaccines in patients with metastatic renal cell carcinoma (RCC) showed immune cell infiltration at vaccine sites and delayed-type hypersensitivity (DTH) responses to autologous tumor cells indicative of T-cell immunity. To further characterize RCC T-cell responses and identify relevant RCC-associated antigens, we did a detailed analysis of CD8+ T-cell responses in two vaccinated RCC patients who generated the greatest magnitude of DTH response and also displayed a strong clinical response to vaccination (>90% reduction in metastatic tumor volume). Three separate CD8+ T-cell lines (and subsequent derived clones) derived from patient 24 recognized distinct RCC-associated antigens. One recognized a shared HLA-A*0201-restricted antigen expressed by both renal cancer cells and normal kidney cells. This recognition pattern correlated with a positive DTH test to normal kidney cells despite no evidence of impairment of renal function by the patient's remaining kidney after vaccination. A second line recognized a shared HLA-C7-restricted antigen that was IFN-gamma inducible. A third line recognized a unique HLA-A*0101-restricted RCC antigen derived from a mutated KIAA1440 gene specific to the tumor. In addition, two independent CTL lines and three clones were also generated from patient 26 and they recognized autologous tumor cells restricted through HLA-A*0205, HLA-A/B/C, and HLA-B/C. These results show that paracrine granulocyte-macrophage colony-stimulating factor tumor vaccines may generate a diverse repertoire of tumor-reactive CD8+ T-cell responses and emphasize the importance of polyvalency in the design of cancer immunotherapies.

Amino Acid Sequence↗

Metal ion modulated organization and function of the Langmuir-Blodgett films of amphiphilic diacetylene: photopolymerization, thermochromism, and supramolecular chirality.

Some novel properties of organized molecular films of 10,12-tricosadiynoic acid (TDA), which were modulated by transition metal ions, were investigated. It was found that metal ions such as Cu(2+), Zn(2+), Ni(2+), Cd(2+), and Ag(+) in the subphase can greatly affect the monolayer formation of TDA and the properties of the subsequently deposited Langmuir-Blodgett (LB) films, particularly in the case of Ag(+), Zn(2+), and Cu(2+) ions. TDA LB film from the subphase containing Ag(+) ion could not be photopolymerized. It was suggested that both the strong chelating property to the carboxylate and the easy reduction of Ag(+) in the film disrupted the topochemical sequence of TDA and resulted in no polymerization in the film. Zinc ion coordinated TDA film could be photopolymerized into a blue polydiacetylene (PDA) film, which showed a reversible thermochromism between blue and purple color upon thermal stimulation. Fourier transform infrared spectra revealed the difference of the Zn(2+)-PDA film from those of the other ions, and the mechanism of the thermochromism was discussed. Copper ion coordinated TDA film could only be photopolymerized to a red PDA film, which showed supramolecular chirality although TDA itself was achiral. Atomic force microscopic measurements revealed the nanofiber structure in the Cu(2+)-PDA film. The supramolecular chirality of the Cu(2+)-PDA film was suggested to be due to the arrangement of the polymer backbone in a helical sense. Furthermore, it was found that the chiral assemblies from the achiral TDA molecules were very stable and the chirality could be kept even upon heating or treating with alkaline solution. While many synthetic efforts have been devoted to the functionalization of PDA films, we provided a simple method of modulating the organization and function of PDA films through metal ions.

Fatty Acids, Unsaturated↗

Effects of growth hormone and/or sex steroid administration on whole-body protein turnover in healthy aged women and men.

Aging is associated with reduced activities of the growth hormone (GH), insulin-like growth factor I (IGF-I), and sex steroid axes, and with decreased lean body mass and protein synthesis. Using a randomized, double-blinded, placebo-controlled design, we studied the effects of 6 months of administration of GH alone, sex hormone alone (hormone replacement therapy in women, testosterone enanthate [T] in men), or GH plus sex hormone on protein turnover in healthy men (n=60) and women (n=43), aged 65 to 88 years (mean, 71+/-4.4 years). Growth hormone administration significantly increased IGF-I levels in both sexes, more markedly in men. Sex steroid administration increased the levels of estrogen and testosterone in women and men, respectively (P=.05). Protein turnover was measured before and after the 26-week treatment period by means of a primed, constant l-[1-(13)C]leucine infusion. In men, GH plus T administration increased leucine flux from 80.2+/-2.8 to 93.6+/-4.2 micromol.h-1.kg-1 (P=.02). Leucine oxidation did not change significantly after hormone treatment in either sex. Growth hormone treatment led to nonsignificant upward trends in nonoxidative leucine disposal in men (9.1+/-5.2 mol.h-1.kg-1) and women (7.6+/-7.1 mol.h-1.kg-1). Among all groups combined, changes in nonoxidative leucine disposal were directly related to those of serum IGF-I level (r=0.248, P<.02). Whole-body protein turnover increased in GH plus T-treated men (0.6+/-0.2 g protein.kg-1.d-1; P<.01). These data suggest that low-dose GH administration increases protein synthesis in healthy aged women and men, and that the coadministration of testosterone plus GH enhances this effect in elderly men.

Aged↗