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Results for “functional profiling”

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At least 1,351 records · Page 75Linked to original sources
PubMed2003

Comparative effects of oral esterified estrogens with and without methyltestosterone on endocrine profiles and dimensions of sexual function in postmenopausal women with hypoactive sexual desire.

OBJECTIVE: In some women, a decline in sexual interest accompanies a relative androgen insufficiency after menopause. We sought to characterize the hormonal effects of the combination of oral esterified estrogens and methyltestosterone and to investigate whether this regimen improves hypoactive sexual desire. DESIGN: Double-blind randomized trial. SETTING: Healthy volunteers in a multicenter research environment. PATIENT(S): Postmenopausal women taking estrogen therapy who were experiencing hypoactive sexual desire. INTERVENTION(S): 4 months of treatment with 0.625 mg of esterified estrogens (n = 111) or the combination of 0.625 mg of esterified estrogens and 1.25 mg of methyltestosterone (n = 107). MAIN OUTCOME MEASURES: Baseline and end-of-study measurements of total and bioavailable testosterone and sex hormone-binding globulin (SHBG), and mean change in level of sexual interest or desire as rated on the Sexual Interest Questionnaire. RESULT(S): Treatment with the combination of esterified estrogens and methyltestosterone significantly increased the concentration of bioavailable testosterone and suppressed SHBG. Scores measuring sexual interest or desire and frequency of desire increased from baseline with combination treatment and were significantly greater than those achieved with esterified estrogens alone. Treatment with the combination was well tolerated. CONCLUSION(S): Increased circulating levels of unbound testosterone and suppression of SHBG provide a plausible hormonal explanation for the significantly improved sexual functioning in women receiving the combination of esterified estrogen and methyltestosterone.

Administration, Oral↗
PubMed2004

A randomised, controlled, triple-blind trial of the efficacy of homeopathic treatment for chronic fatigue syndrome.

OBJECTIVE: There is no management regime for chronic fatigue syndrome (CFS) that has been found to be universally beneficial and no treatment can be considered a "cure". Patients with CFS may use complementary and alternative medicine (CAM). Our aim was to evaluate homeopathic treatment in reducing subjective symptoms of CFS. METHOD: Using a triple-blind design (patient and homeopath blind to group assignment and data analyst blind to group until after initial analyses to reduce the possibility of bias due to data analyst), we randomly assigned patients to homeopathic medicine or identical placebo. One hundred and three patients meeting the Oxford criteria for CFS were recruited from two specialist hospital out patient departments. Patients had monthly consultations with a professional homeopath for 6 months. Main outcome measures were scores on the subscales of the Multidimensional Fatigue Inventory (MFI) and proportions of each group attaining clinically significant improvements on each subscale. Secondary outcome measures were the Fatigue Impact Scale (FIS) and the Functional Limitations Profile (FLP). Ninety-two patients completed treatment in the trial (47 homeopathic treatment, 45 placebo). Eighty-six patients returned fully or partially completed posttreatment outcome measures (41 homeopathic treatment group who completed treatment, 2 homeopathic treatment group who did not complete treatment, 38 placebo group who completed treatment, and 5 placebo group who did not complete treatment). RESULTS: Seventeen of 103 patients withdrew from treatment or were lost to follow-up. Patients in the homeopathic medicine group showed significantly more improvement on the MFI general fatigue subscale (one of the primary outcome measures) and the FLP physical subscale but not on other subscales. Although group differences were not statistically significant on four out of the five MFI subscales (the primary outcome measures), more people in the homeopathic medicine group showed clinically significant improvement. More people in the homeopathic medicine group showed clinical improvement on all primary outcomes (relative risk=2.75, P=.09). CONCLUSIONS: There is weak but equivocal evidence that the effects of homeopathic medicine are superior to placebo. Results also suggest that there may be nonspecific benefits from the homeopathic consultation. Further studies are needed to determine whether these differences hold in larger samples.

Adult↗
PubMed2004

Substance P axons and sensory threshold increase in burn-graft human skin.

BACKGROUND: Our knowledge of afferent nerve fiber reinnervation of grafted skin following third-degree burn is limited by a lack of quantitative histological and psychophysical assessment from the same cutaneous area. The current study compares fiber profile and functional recovery measurements in injured and control skin from the same subject. MATERIALS AND METHODS: Nerve regeneration and modality-specific sensory thresholds were compared using immunocytochemical labeling with protein gene product 9.5 antibody to stain all axons and anti-substance P to label substance P axons (which are predominantly unmyelinated), as well as computerized instrumentation to obtain psychophysical estimates. RESULTS: Compared to control skin, threshold measures of pinprick (P < 0.001), warming (P < 0.001), touch (P < 0.001), and vibration (P < 0.01) were significantly elevated in burn-graft skin and correlated with histological analysis of skin biopsies obtained from the same site. Immunohistochemical staining of all axons innervating the dermis and epidermis revealed a significant reduction in burn-graft relative to control skin (54% decrease, P < 0.0001). In contrast, the incidence of substance P nerve fibers was significantly elevated in burn-graft (177% increase, P < 0.05) and appeared to correlate with patient reports of pruritus and pain. CONCLUSIONS: Observations support the hypothesis that sensory regeneration is fiber-size-dependent in burn-graft skin. The findings that substance P fiber growth increased while total fiber count decreased and that thermal threshold showed the greatest degree of functional recovery suggest that unmyelinated neurons have the greater ability to transverse scar tissue and reinnervate grafted skin following third-degree burn injury.

Adult↗
PubMed2004

[Basics of esthetic and functional cephalometric analysis of the profile].

We report a new cephalometric method for profile analysis, which uses strictly exobasicranial landmarks: 13 anatomic points, 9 bone points and 4 skin points. The analysis is based on phylogenetic, ontogenetic, anatomic and biomechanical data. Phylogenetic analysis reveals that the occipital plate belongs more to the cranial vault than the base of the skull. Embryology shows that on the midline the facial skull base ends at the spheno-occipital suture and that the overall skull base ends at the basion. The pre-maxillary fuses rapidly to the maxillary, while the pterygoid processes, which belong to the face and not the skull base, fusion very rapidly to the skull base. Revisiting the anatomy of the facial skull base shows that it is prolonged posteriorly medially to meast the synostosic creast and latterally to the glenoid fossae. Further anatomic analysis shows that the dentate and muscular part of the superior level of the facial mass correspond to equivalent parts of the inferior mandibular level. The biomechanical analysis reveals that the anterior pillar passes through the pre-maxillary, ending on the supra-orbital border and the glabella and as such belongs to the face. The posterior pillar follows the pterygoid process ending in the sphenoid. The glabella and these two pillars are taken into account in this new analysis technique.

Adult↗
PubMed2003

Rosiglitazone improves glucose metabolism in nondiabetic uremic patients on CAPD.

BACKGROUND: Insulin resistance, a strong risk factor for atherosclerotic vascular disease, is present in uremic patients without diabetes on continuous ambulatory peritoneal dialysis (CAPD) therapy. Amelioration of insulin resistance may reduce associated long-term cardiovascular complications. The aim of the study is to investigate the effects of rosiglitazone (ROS), an insulin sensitizer, on glucose metabolism in CAPD patients without diabetes. METHODS: Fifteen uremic patients without diabetes on CAPD therapy were enrolled. All were administered ROS, 4 mg/d, for 12 weeks. A control group consisted of 15 age- and sex-matched healthy subjects. Oral glucose tolerance test (OGTT) results, fasting glucose and insulin levels, related blood biochemistry results, and C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels were determined before initiation and at 4 and 12 weeks of therapy. Insulin resistance was evaluated using the homeostasis model assessment method (HOMA-IR). A whole-body insulin sensitivity index (ISI) and insulinogenic index for insulin production were calculated from OGTT results. RESULTS: CAPD patients showed significantly greater HOMA-IR and glucose intolerance compared with healthy controls. After 4 and 12 weeks of ROS therapy, there were no significant changes in body weight, blood pressure, dialysis adequacy, hemoglobin level, hemoglobin A(1c) level, liver function, lipid profile, or intact parathyroid hormone, CRP, IL-6, or TNF-alpha levels. There was a significant decrease in HOMA-IR (3.2 +/- 0.6, 2.2 +/- 0.4, and 2.1 +/- 0.4; P < 0.05). During the OGTT, there was a significant decrease in the area under the glucose curve and a significant increase in ISI (3.5 +/- 0.4, 5.0 +/- 0.7, and 5.3 +/- 0.7; P < 0.05), but no significant change in insulinogenic index. CONCLUSION: ROS improved insulin resistance in CAPD patients without diabetes. Whether long-term use of ROS reduces cardiovascular risk needs further study.

Adult↗
PubMed2003

Expectant management of severe preeclampsia and preeclampsia superimposed on chronic hypertension between 24 and 34 weeks' gestation.

BACKGROUND: Timing of delivery is difficult to judge in preeclampsia. OBJECTIVE: To compare the differences of maternal and perinatal outcome of patients with severe preeclampsia and essential hypertension with superimposed preeclampsia, with expectant management at 24-34 weeks' gestation. STUDY DESIGN: A retrospective review of a conservative regime using intravenous magnesium sulfate, glucocorticoids and antihypertensive drugs, monitored by serial liver function tests, full blood count, coagulation profile, and renal function tests. Fetal status was assessed by daily non-stress test and ultrasound twice by week. RESULTS: A total number of 100 women had severe preeclampsia and 29 superimposed preeclampsia. The average pregnancy prolongation was 8.4 and 8.5 days, respectively. Oliguria, abruption placentae and HELLP syndrome were frequent complications similar in each group. There were no cases of eclampsia or disseminated coagulopathy in either group. The total neonatal survival rate was 93% in both groups. CONCLUSION: Expectant management is equally safe in both superimposed preeclampsia and severe preeclampsia of early onset.

Antihypertensive Agents↗
PubMed2003

Cloning and characterization of human CADPS and CADPS2, new members of the Ca2+-dependent activator for secretion protein family.

The recent identification of some of the components involved in regulated and constitutive exocytotic pathways has yielded important insights into the mechanisms of membrane trafficking and vesicle secretion. To understand precisely the molecular events taking place during vesicle exocytosis, we must identify all of the proteins implicated in these pathways. In this paper we describe the full-length cloning and characterization of human CADPS and CADPS2, two new homologs of the mouse Cadps protein involved in large dense-core vesicle (LDCV)-regulated exocytosis. We show that these two genes have disparate RNA expression patterns, with CADPS restricted to neural and endocrine tissues and CADPS2 expressed ubiquitously. We also identify a C2 domain, a known protein motif involved in calcium and phospholipid interactions, in both CADPS and CADPS2. We propose that CADPS functions as a calcium sensor in regulated exocytosis, whereas CADPS2 acts as a calcium sensor in constitutive vesicle trafficking and secretion. CADPS and CADPS2 were determined to span 475 kb and 561 kb on human chromosomes 3p21.1 and 7q31.3, respectively. The q31-q34 of human chromosome 7 has recently been identified to contain a putative susceptibility locus for autism (AUTS1). The function, expression profile, and location of CADPS2 make it a candidate gene for autism, and thus we conducted mutation screening for all 28 exons in 90 unrelated autistic individuals. We identified several nucleotide substitutions, including only one that would affect the amino acid sequence. No disease-specific variants were identified.

Amino Acid Sequence↗
PubMed1999

Subjective quality of life in schizophrenic patients living in the community. Relationship to clinical and social characteristics.

The aims of this study were to assess the quality of life among 120 schizophrenic patients who were attending a psychiatric outpatient department and to investigate which socio-demographic and clinical factors influenced their subjective quality of life. Quality of life was assessed by the Lanchashire quality of life profile, social functioning was judged according to the Global Assessment of Functioning (GAF) scale, and psychopathology was rated by means of the Brief Psychiatric Rating Scale (BPRS). Both objective and subjective life conditions indicated an impaired quality of life for the patients. The areas of finance and work had the largest proportion of dissatisfied patients. Socio-demographic indicators showed to have a weak influence on the patient's self-assessed quality of life while clinical factors, such as psychopathology, strongly influenced the patient's life satisfaction. It is concluded that there is a need for further emphasise on the clinical, financial, and social interventions for this group of patients.

Ambulatory Care↗
PubMed2000

Stimulus- and cell-type-specific regulation of CCAAT-enhancer binding protein isoforms in glomerular mesangial cells by lipopolysaccharide and cytokines.

Binding sites for the CCAAT-enhancer binding protein (C/EBP) family are present in the promoter regions of several genes that are known to be expressed by mesangial cells (MC) during the pathogenesis of glomerular inflammatory diseases. The precise regulation of the C/EBP family by agents that are known to activate MC is, however, poorly understood. We report here the action of interleukin-1 (IL)-1 and, for the first time, lipopolysaccharide (LPS), platelet-derived growth factor (PDGF), IL-6, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) on the C/EBP expression profile and functional DNA binding activity in primary rat MC. Both cell-type- and stimulus-specific regulation of C/EBP mRNA expression and DNA binding activity were identified, with C/EBPalpha being induced by LPS, C/EBPbeta by LPS, IL-1, TNF-alpha and C/EBPdelta by LPS, IL-1, IFN-gamma, TNF-alpha and PDGF. Such differential regulation, particularly that of C/EBPbeta, may be responsible for the mediator-specific differences in the expression of C/EBP-regulated genes in MC. Additionally, the involvement of potential post-transcriptional mechanisms in the regulation of C/EBPdelta were identified. These studies provide novel insights into the stimulus-specific regulation of gene expression during renal diseases.

Animals↗
PubMed1999

Identification and characterization of allergens in two species of tuna fish.

BACKGROUND: In countries where fish consumption is high, allergenic reactions to fish are common among patients diagnosed with food hypersensitivity. For tuna fish, allergenic proteins are not known. In addition, it is not known how the tuna fish extracts should be processed to obtain optimal in vitro diagnostic performance and to preserve labile antigens. OBJECTIVE: The aim of this study was to characterize IgE-binding components of Yellowfin and Albacore tuna fish. METHODS: Various tuna fish extract preparations were fractionated by sodium dodecylsulfate-polyacrylamide gel electrophoresis and transferred to nitrocellulose and analyzed by using tuna positive patients with different Western blot profiles. The functional activity of the extracts was evaluated by basophil histamine release. RESULTS: Immunoblot analysis showed the majority of patients responding to Yellowfin tuna extract. Inhibition studies using immunoblot analysis and histamine release testing showed a specific protein with a molecular weight of approximately 46 kD that is present in Yellowfin tuna, but absent in Albacore. Only defatted, lyophilized tuna fish extracts were able to induce histamine release from sensitized basophils although IgE-binding components were detected in fresh raw, fresh cooked, and canned tuna fish preparations. CONCLUSION: These studies indicate that patient sera may contain different tuna fish species IgE specific antibodies directed against unique species specific allergens present in Yellowfin and Albacore tuna fish. Possibly, extracts should contain specific allergenic components from both Albacore and Yellowfin to cover the epitope heterogeneity observed in sera from patients developing IgE antibodies against tuna fish.

Allergens↗
PubMed2001

Effects of drugs on the autonomic control of short-term heart rate variability.

The autonomic nervous system links the brain and the heart. Efferent links in the neural control of the heart consist of sympathetic and parasympathetic (vagal) fibers innervating the sinus node. Because sympathetic and vagal firing alter spontaneous sinus node depolarization, cardiac rate and rhythm convey information about autonomic influences on the heart. The easy availability of ECG rendered possible the assessment of sinus rhythm as an index of autonomic outflow. The frequency-domain approach uses non-invasive recordings and appears to provide a quantitative evaluation of the autonomic modulation of cardiovascular function. Spectral profiles resulting from vagal or sympathetic blockades at the cardiac (or vascular) level might be used as references to unravel the mechanism of action of the drug under examination. A more comprehensive assessment will be obtained if spectral analysis is used as a complement to existing techniques applied for describing the neurohumoral status of patients (microneurographic recordings, norepinephrine spillover). This review also reports some pitfalls encountered in variability studies.

Autonomic Agents↗
PubMed2026

Selective Enrichment of Newly Synthesized Proteins Using Phos-Tag Click Tip Enables Nascent Proteome Analysis in Influenza A Virus Infection.

Profiling of newly synthesized proteins (NSPs) provides access to dynamic changes in protein production that accompany acute cellular responses. Bioorthogonal noncanonical amino acid tagging (BONCAT)-based approaches enable selective labeling of NSPs; however, their broader application remains constrained by labor-intensive enrichment workflows and limited sensitivity for direct peptide-level analysis. Here, we developed a workflow termed "Phos-tag Click Tip" by integrating a phosphorylated variant of bicyclononyne (pBCN) with Phos-tag affinity purification to selectively capture azidohomoalanine (AHA)-labeled peptides for newly synthesized proteome analysis (NSProteomics). This approach overcomes key limitations of conventional proteomics and BONCAT-based strategies by enabling efficient enrichment and sensitive detection of NSP-derived peptides. Using this workflow, we performed comprehensive NSP profiling of host cells during influenza A virus infection. We identified dynamic changes in distinct NSP profiles associated with viral replication, host restriction, and immune responses, many of which were not readily detected with conventional whole-cell- or phospho-proteomic analyses. Overall, the Phos-tag Click Tip workflow provides a complementary approach for stimulus-responsive NSP profiling, offering functionally relevant insights into host-virus interactions and cellular response mechanisms.

Proteome↗
PubMed2026

Synthesis and Application of a Suite of 2,5-Aryl Tetrazole Photoaffinity-Based Probes for Profiling Microbial Carbohydrate and Mucin Metabolism in Gut Microbiota.

Photoaffinity-based chemoproteomics provides a strategy for interrogating protein engagement and networks within complex biological systems. In the context of carbohydrate metabolism, however, linking the probe structure to glycan-processing networks remains challenging due to the diversity and redundancy of carbohydrate-active enzymes (CAZymes). Here, we employ 2,5-tetrazoles as photoreactive groups to develop a suite of monosaccharide-bearing probes designed to capture carbohydrate-associated protein environments in gut microorganisms. Across defined bacterial cultures and human fecal lysates, tetrazole probes enriched glycoside hydrolases (GHs) and additional carbohydrate-associated proteins, including transporters and regulatory elements. Notably, enrichment profiles were functionally biased toward glycan-processing modules, despite minimal shifts in global protein abundance under different growth conditions. These findings demonstrate that tetrazole chemoproteomics complements abundance-based proteomics by reporting on glycan-associated protein engagement and organization. Together, this probe suite provides a substrate-centric approach to studying carbohydrate-processing networks in defined microbes and complex microbiomes.

Tetrazoles↗
PubMed1993

Probing biomembrane interfacial potential and pH profiles with a new type of float-like fluorophores positioned at varying distance from the membrane surface.

Fluorophores of a new type were synthesized to probe the electrostatic potential or pH profiles in the external interface of biomembranes. The probes consist of the pH-sensitive fluorophore 7-hydroxycoumarin, coupled to a tetradecyl (myristyl) tail by a spacer group of varying length. A positively charged group is included between the tetradecyl and spacer groups to encourage a float-like alignment in the membrane head-group region. Three probes of this type were compared with 4-heptadecyl-7-hydroxycoumarin the fluorophore of which is embedded in the lipid head-group domain. Thus, a ruler-type positioning of the fluorophores was obtained at about 0.2, 0.6, 1.0, and 1.3 nm from the surface. The membrane-bound probes were tested in well-defined liposomes prepared by extrusion with different surface charge densities and size. The predicted positioning of the float-like probes is supported by their binding behavior in liposomes and by steady-state and nanosecond time-resolved fluorescence anisotropy, as well as by their accessibility to different quenchers. The interfacial electrostatic potential (psi d) and pH (pHd) values were derived from the observed apparent pKa shifts of the probes. The obtained psi d and pHd profiles as function of the surface potential (psi 0) and distance from the membrane surface are in good harmony with predictions from nonlinear Gouy-Chapman theory. The electrokinetic potentials (zeta) of the liposome series, measured by Doppler-electrophoretic frequency shift of laser light scattering, are in good proportion to the probe data. When bound to yeast cells, these probes monitor interfacial changes in parallel with glucose-induced medium acidification.(ABSTRACT TRUNCATED AT 250 WORDS)

Fluorescence Polarization↗
PubMed2004

Novel N-arylpyrazolo[3,2-c]-based ligands for the glucocorticoid receptor: receptor binding and in vivo activity.

A novel series of selective ligands for the human glucocorticoid receptor (hGR) are described. Preliminary structure-activity relationships were focused on substitution at C-1 and indicated a preference for 3-, 4-, and 5-substituted aromatic and benzylic groups. The resulting analogues, e.g., 18 and 34, exhibited excellent affinity for hGR (IC(50) 1.9 nM and 2.8 nM, respectively) and an interesting partial agonist profile in functional assays of transactivation (tyrosine aminotransferase, TAT, and glutamine synthetase, GS) and transrepression (IL-6). The most potent compounds described in this study were the tertiary alcohol derivatives 21 and 25. These candidates showed highly efficacious IL-6 inhibition versus dexamethasone. The thiophenyl analogue 25 was evaluated in vivo in the mouse LPS challenge model and showed an ED(50) = 4.0 mg/kg, compared to 0.5 mg/kg for prednisolone in the same assay.

Animals↗
PubMed1998

The psychosocial health status of carers of persons with dementia: a comparison with the chronically ill.

This project aimed to determine overall psychosocial health (measured using the psychosocial dimension of the Functional Limitations Profile) and factors which influence this in a group of carers of those with dementia and to compare their psychosocial health with that of older people attending general practitioners (GPs); arthritis support groups and a pain clinic (out-patients) and a group of community dwellers undergoing renal dialysis. The carer group showed a significant decrease in recreation and pastimes and social interactions compared to older GP attenders. The carers showed similar restrictions in social interactions and recreation to those with chronic arthritis, but the latter were more impaired in the domains of emotional behaviour and sleep and rest. The older people attending a pain clinic did not differ in the areas of alertness and social interactions compared to the carer group. The dialysis group demonstrated the greatest dysfunction overall. These results suggest that the psychosocial health of carers of those with dementia is impaired, the profile of which differs from those suffering with chronic diseases. Social and recreation activities appear most affected in the carers. Commensurate with studies exploring the health status of those suffering from diseases, the measurement of the psychosocial health status of carers should also be considered in the scope of assessment and intervention.

Analysis of Variance↗
PubMed1997

T cell mechanisms in experimental autoimmune uveoretinitis: susceptibility is a function of the cytokine response profile.

This study addresses the question whether susceptibility versus resistance to experimental autoimmune uveoretinitis (EAU) is connected to a Th1-type (interferon-gamma high, interleukin-4 low), versus a Th2-type (IFN-gamma low, IL-4 high) response. Primed lymph node cells of susceptible Lewis rats produced IFN-gamma in response to antigen in culture and transferred EAU to syngeneic recipients, whereas lymph node cells of resistant F344 rats made no IFN-gamma and did not transfer disease. Reversal of the disease pattern, by treatment of F344 rats with B. pertussis toxin and immunisation of Lewis rats with antigen in incomplete Freund's adjuvant, resulted in a parallel reversal of these response patterns. Neither strain produced significant IL-4 responses. A study of the response patterns in mice confirmed that high Th1 responders were susceptible, whereas low Th1 responders and Th2 responders were resistant. We conclude that susceptibility to EAU is connected with a Th1-dominant response, but resistance can involve either a 'null', F344-like response (Th1-low/Th2-low) or a Th2-dominant response.

Adoptive Transfer↗
PubMed2004

Isolation of highly pure alveolar epithelial type I and type II cells from rat lungs.

There are no ideal cell lines available for alveolar epithelial type I and II cells (AEC I and II) at the present time. The current methods for isolating AEC I and II give limited purities. Here, we reported improved and reproducible methods for the isolation of highly pure AEC I and II from rat lungs. AEC I and II were released from lung tissues using different concentrations of elastase digestion. Macrophages and leukocytes were removed by rat IgG 'panning' and anti-rat leukocyte common antigen antibodies. For AEC II isolation, polyclonal rabbit anti-T1alpha (an AEC I apical membrane protein) antibodies were used to remove AEC I contamination. For AEC I isolation, positive immunomagnetic selection by polyclonal anti-T1alpha antibodies was used. The purities of AEC I and II were 91 +/- 4 and 97 +/- 1%, respectively. The yield per rat was approximately 2 x 10(6) for AEC I and approximately 33 x 10(6) for AEC II. The viabilities of these cell preparations were more than 96%. The protocol for AEC II isolation is also suitable to obtain pure AEC II (93-95%) from hyperoxia-injured and recovering lungs. The purified AEC I and II can be used for gene expression profiling and functional studies. It also offers an important tool to the field of lung biology.

Animals↗