Biomedical subjects

C L Yu

Publications and source records attributed to C L Yu.

At least 55 records · Page 3Linked to original sources

PubMed1998

The local addition of tenoxicam reduces the incidence of low back pain after lumbar epidural anesthesia.

BACKGROUND: Postepidural backache is a common postoperative complaint after lumbar epidural anesthesia. Useful interventions to decrease the incidence of postepidural backache would be helpful. METHODS: We performed a prospective, randomized, double-blind study to compare the effect of local addition of tenoxicam on the incidence of postepidural backache after nonobstetric surgery. One thousand unpremedicated ASA physical status I or II patients scheduled for hemorrhoidectomy were assigned randomly to tenoxicam or control groups. Patients in the control group received 25 ml lidocaine, 2%, with epinephrine 1:200,000 epidurally and 4 ml lidocaine, 1%, for local skin infiltration. Patients in the tenoxicam group received 25 ml lidocaine, 2%, with epinephrine 1:200,000 epidurally and 4 ml lidocaine, 1%, with tenoxicam (2 mg) 1:2,000 for local skin infiltration. Patients were interviewed at 24, 48, and 72 h postoperatively using a standard visual analog scale for evaluation of postepidural backache. A patient was considered to have postepidural backache when the postoperative visual analog scale score was higher than the preoperative score. RESULTS: The incidence of postepidural backache in patients in the control group for the 3 days were 22.8%, 17.4%, and 9.2%, all of which were significantly more frequent than observed in the patients in the tenoxicam group (6.8%, 4.0%, and 1.2%, P < 0.01). There was a significant association between backache and multiple attempts at epidural needle insertion. CONCLUSION: In summary, the local addition of tenoxicam reduced the incidence and severity of postepidural backache.

Adolescent↗

PubMed1997

Constitutive activation of the Janus kinase-STAT pathway in T lymphoma overexpressing the Lck protein tyrosine kinase.

The Lck protein, a Src family tyrosine kinase, plays a critical role in T cell maturation and activation. Dysregulation of Lck expression or Lck kinase activity has been implicated in T cell leukemias from mice to humans, although the mechanism underlying Lck-mediated oncogenesis is still largely unclear. We report here that both DNA binding activities and tyrosine phosphorylation of STAT3 and STAT5, but not STAT1, are constitutively enhanced in the mouse T cell lymphoma LSTRA, which is a well-characterized cell line that overexpresses Lck protein and exhibits high levels of Lck kinase activity. Furthermore, Janus kinase 1 (jak1) and Jak2 protein tyrosine kinases are constantly activated in these cells, as determined by their autophosphorylation in an in vitro kinase assay and increased levels of tyrosine phosphorylation on immunoblots. Therefore, like Src-transformed cells, Lck-overexpressing LSTRA cells also exhibit constitutive activation of distinct Jak and STAT proteins.

3T3 Cells↗

PubMed1997

The tumor suppressor p53 is a negative regulator of estrogen receptor signaling pathways.

The estrogen receptor (ER) is a ligand-dependent transcription factor which regulates growth, development, differentiation and reproduction. To test the hypothesis that the diverse effects of the ER could be mediated by interacting with other transcription factors/oncogenes, the present study assessed its interaction with the tumor suppressor p53. p53 is a transcription factor which is involved in cell cycle regulation and apoptosis. We found that the wild-type p53 physically interacted with ER in vivo and repressed the estrogen-activated transcriptional activity. However, p53 mutants had no or reduced repression effect, depending on the sites of mutation. These findings suggest that p53 can cross talk with the ER in hormone-activated signaling pathways in cells.

Endometrial Neoplasms↗

PubMed1997

Involvement of proteasomes in regulating Jak-STAT pathways upon interleukin-2 stimulation.

Interleukin-2 (IL-2) activates the receptor-associated Janus family tyrosine kinases, Jak1 and Jak3, which in turn phosphorylate and activate specific STAT proteins (signal transducers and activators of transcription), such as STAT5. Activation of Jak and STAT proteins by IL-2 is transient and the mechanism for the subsequent down-regulation of their activity is largely unknown. We report here that IL-2-induced DNA-binding activity and tyrosine phosphorylation of STAT5 are stabilized by a proteasome inhibitor MG132; however, no detectable ubiquitination of the STAT proteins is observed. This sustained STAT5 activation can be blocked by protein kinase inhibitors, which is consistent with the ability of the proteasome inhibitor to stabilize IL-2-induced tyrosine phosphorylation of Jak1 and Jak3. These results suggest that proteasome-mediated protein degradation modulates protein-tyrosine phosphatase activity that negatively regulates the Jak-STAT signaling pathways.

Cell Line↗

PubMed1997

The expression of genes modulating programmed cell death in normal human polymorphonuclear neutrophils.

Normal human polymorphonuclear neutrophils (PMN) have a short life and die in progression via apoptosis. In order to understand the molecular basis of PMN apoptosis, the expression of apoptosis-related (Fas, Fas-ligand, p53, and c-myc) and survival-related (bcl-2) genes was detected by flow cytometry, Western blot and reverse transcription-assisted polymerase chain reaction (RT-PCR). We found that Fas and Fas-ligand (FasL) were expressed on the surface of most of the cells. However, the disappearance of FasL was much faster than Fas after 24 h incubation. p53 and bcl-2 were also expressed in the cytoplasm of most of the cells. In contrast, the expression of c-myc was negligible in PMN. The addition of monoclonal anti-human Fas antibody (25 micrograms/ml) to PMN suspension enhanced whereas anti-FasL antibody (25 micrograms/ml) suppressed PMN apoptosis in 48 h incubation. These results suggest that the activation of Fas pathway induced by Fas-FasL interaction among PMNs is one of the mechanisms for spontaneous PMN apoptosis. Lack of proto-oncoprotein c-myc expression in PMN is responsible for their non-proliferative property and may aggravate the spontaneous apoptosis of the cells.

Animals↗

PubMed1997

Role of epidermal growth factor receptor and STAT-3 activation in autonomous proliferation of SUM-102PT human breast cancer cells.

This report describes the isolation and characterization of a new human breast cancer cell line, SUM-102PT, obtained from a minimally invasive human breast carcinoma. SUM-102PT cells have a near diploid karyotype, and early-passage cells had minor chromosomal abnormalities including a 5, 12 and a 6, 16 reciprocal translocation. The cells were isolated and have been continually cultured in three defined media, one of which contains exogenous epidermal growth factor (EGF). SUM-102PT cells have also been carried in an EGF-free medium supplemented with progesterone. All SUM-102PT cells require EGF receptor (EGFR) activation for continuous growth, because incubation of the cells with EGFR-neutralizing antibodies or with EGFR kinase inhibitors blocks growth of these cells. Southern analysis indicates that the EGFR gene is not amplified in these cells; however, these cells express high levels of EGFR mRNA. Thus, SUM-102PT is representative of a class of human breast cancers characterized by high level EGFR expression in the absence of gene amplification. SUM-102PT cells cultured in EGF-free, progesterone-containing medium express high levels of constitutively active EGFR. Conditioned medium from SUM-102PT cells contains an EGF-like mitogen that binds to a heparin-agarose affinity matrix with high affinity. Northern analysis for various EGF family members indicates that SUM-102PT cells synthesize heparin binding (HB)-EGF mRNA. HB-EGF protein is detectable on the surface of these cells by immunohistochemistry, and SUM-102PT cells are killed by diphtheria toxin, which acts by binding to HB-EGF. Furthermore, HB-EGF antibodies partially neutralize the mitogenic activity of the conditioned medium. Thus, EGFR activation in SUM-102PT cells is mediated, at least in part, by autocrine/juxtacrine stimulation by HB-EGF. SUM-102PT cells also express constitutively active STAT-3 homodimers. Constitutively tyrosine-phosphorylated STAT-3 homodimers were also detected in another breast cancer cell line, MDA468, which has an EGFR amplification and also has constitutive EGFR activity. Thus, SUM-102PT is a new human breast cancer cell line that expresses activated EGFR as a result of an autocrine/juxtacrine interaction with HB-EGF which, in turn, results in activation of STAT-3.

Adenocarcinoma↗

PubMed1997

Evidence for linkage of a candidate chromosome 1 region to human systemic lupus erythematosus.

Genetic susceptibility confers significant risk for systemic lupus erythematosus (SLE). The MHC region and other polymorphic loci have been associated with SLE. Because more compelling evidence for an involvement of a genetic locus includes linkage, we tested a candidate region homologous to a murine SLE susceptibility region in 52 SLE-affected sibpairs from three ethnic groups. We analyzed seven microsatellite markers from the human chromosome 1q31-q42 region corresponding to the telomeric end of mouse chromosome 1, the region where specific manifestations of murine lupus, including glomerulonephritis and IgG antichromatin, have been mapped. Comparing the mean allele sharing in affected sibpairs of each of these seven markers to their expected values of 0.50, only the five markers located at 1q41-q42 showed evidence for linkage (P = 0.0005-0.08). Serum levels of IgG antichromatin also showed evidence for linkage to two of these five markers (P = 0.04), suggesting that this phenotype is conserved between mice and humans. Compared to the expected random distribution, the trend of increased sharing of haplotypes was observed in affected sibpairs from three ethnic groups (P < 0.01). We concluded that this candidate 1q41-q42 region probably contains a susceptibility gene(s) that confers risk for SLE in multiple ethnic groups.

Adolescent↗

PubMed1997

Constitutive activation of JAK1 in Src-transformed cells.

We have previously found that the signal transducer and activator of transcription (Stat) 3 is constitutively activated in cells stably transformed by the v-Src oncoprotein. While activation of Stat proteins has also been observed following epidermal growth factor or platelet-derived growth factor stimulation, Stat3 activation is more commonly associated with signaling through cytokine receptors and activation of the Janus family tyrosine kinases JAK1 or JAK2. We therefore investigated whether JAK1 or JAK2 were activated in Src-transformed cells. In three v-Src-transformed fibroblast cell lines (NIH3T3, Balb/c, and 3Y1), JAK1 displayed increased tyrosyl phosphorylation compared to non-transformed cells. The level of tyrosyl phosphorylation of JAK1 was significantly greater in NIH3T3 cells transformed by expression of v-Src or high levels of a constitutively active mutant of c-Src (Y527F) than in cells overexpressing the less transforming normal c-Src. Enzymatic activity of JAK1 was assessed using autophosphorylation assays. In anti-JAK1 immunoprecipitates from v-Src-transformed NIH3T3 cells, a protein with the same migration as JAK1 showed substantially increased levels of 32P incorporation compared to immunoprecipitates from non-transformed cells. Similar results were obtained using anti-JAK2 immunoprecipitates; however, the level of JAK2 tyrosyl phosphorylation and 32P incorporation in anti-JAK2 immunoprecipitates were markedly lower than in anti-JAK1 immunoprecipitates. We conclude that JAK1, and possibly JAK2, are constitutively activated in Src-transformed cells, raising the possibility that Janus family kinases contribute to the constitutive activation of Stat3 previously observed in these cells and/or other properties of Src-transformed cells.

3T3 Cells↗

PubMed1997

Tamm-Horsfall glycoprotein (THG) is a binder for surface membrane proteins on blood cells and glomerular mesangial cells.

A macromolecule with a molecular weight of 90-100 kDa was purified from normal human pregnancy urine. The molecule was proved to be the Tamm-Horsfall glycoprotein (THG) by Western blot analysis. The macromolecule contains carbohydrate as detected by an enzyme immunoassay. Functionally, the glycoprotein can adhere to and stimulate the thymidine incorporation of human mononuclear cells (MNC) in modest degree via its membranotropic property. In addition to MNC, the protein can also bind to the surface of human polymorphonuclear neutrophils (PMN), red blood cells (RBC) and rat glomerular mesangial cells (RMC). Western blot analysis of various cell lysates with/without proteinase K pretreatment before cell lysis revealed that a 60 kDa and a molecule larger that 94 kDa on the surface of PMN, a 60 kDa protein on MNC and a 32 kDa protein on RBC are the binding molecules for THG. In contrast, many proteins on the surface of RMC could be bound by THG. Immunoprecipitation of membranous iodinated MNC lysates also confirmed that the 60 kDa molecule on MNC is the binding protein for THG. A number of monosaccharide including N-acetylneuraminic acid, N-acetyl-galactosamine, N-acetyl-glucosamine and alpha-methyl-D-mannoside could not inhibit the mitogenic effect of THG on human mononuclear cells. These results suggest that THG is capable of reacting with surface membrane proteins on different cells, but not through the specific carbohydrate-containing lectin-like receptors on the cell surface.

Animals↗

PubMed1997

Alterations in IL-6, IL-8, GM-CSF, TNF-alpha, and IFN-gamma release by peripheral mononuclear cells in patients with active vitiligo.

The purpose of this study was to clarify the relationship between the cellular and humoral immune components in the pathogenesis of vitiligo vulgaris. By using cytokines as indicators of peripheral mononuclear cell (MNC) function, we compared the effects of phytohemagglutinin (PHA) and purified IgG on MNCs derived from patients suffering from active vitiligo with those from normal controls. The results revealed (i) a significant increase in spontaneous production of IL-6 and IL-8 in patients; (ii) PHA, purified IgG from patients (IgG-anti-MC), or IgG from normal controls (N-IgG) induced a significant increase in IL-6 but diminished GM-CSF, TNF-alpha, and IFN-gamma release in patients; and (iii) IgG-anti-MC brought about a significantly higher stimulatory effect on IL-1beta and IFN-gamma production than N-IgG in normal controls. Immunologically, IL-6 can enhance melanocyte ICAM-1 expression, which may increase leukocyte-melanocyte attachment and cause melanocyte damage in vitiligo. A decrease in GM-CSF (an intrinsic growth factor for melanocyte) production may retard recovery from vitiligo by checking the proliferation of surviving melanocytes. A significant decrease in TNF-alpha and IFN-gamma production may partially explain the reduced inflammatory reaction in vitiliginous lesions. That IgG-anti-MC stimulates an increase in IL-1beta and IFN-gamma production in controls suggests that IgG-anti-MC may play a role in melanocyte destruction mediated by monocytes.

Antibodies↗

PubMed1997

The inhibitory effect of UVB irradiation on the expression of p53 and Ki-67 proteins in arsenic-induced Bowen's disease.

The aim of this study is to evaluate the effect of ultraviolet B (UVB) on arsenic-induced Bowen's disease. Four patients were irradiated with 750 mJ/cm2 of UVB and biopsies were performed before treatment and 2 weeks later. Immunohistochemical stains of p53 and Ki-67 were compared by the labelled-streptavidin method before and after the UVB treatment. We found that the number of p53 and Ki-67 positive cells after the UVB treatment were significantly fewer than those of non-UVB-treated specimens. These results suggest that the UVB inhibitory effect in Bowen's disease needs further studies to clarify its value in potentially retarding the progression of the hyperproliferative status in overt skin cancer on a molecular basis.

Arsenic↗

PubMed1997

Pure red cell aplasia in a man with RA.

A 65 year-old man with long-standing rheumatoid arthritis (RA) developed pure red cell aplasia (PRCA), which was apparently not caused by drugs or viral infections. The condition responded favorably to danazol in combination with sulfasalazine. This was probably the 2nd case of RA with PRCA in a male patient.

Aged↗

PubMed1997

Activation of extracellular signal-regulated kinase (ERK) by mitogenic stimuli is repressed in v-Src-transformed cells.

Stimulation of mitogenic signaling pathways results in transient activation of the extracellular signal-regulated kinase (ERK) subfamily of mitogen-activated protein kinases (MAPK) in normal cells. We demonstrate here that activation of ERKs in response to serum or phorbol ester stimulation was markedly repressed in three different rodent fibroblast cell lines stably transformed by v-Src. Activation of the MAPK/ERK kinase (MEK) was also repressed in v-Src-transformed cells, indicating that the repression occurs upstream of ERK. Consistent with repression occurring predominantly at the level of MEK, the phosphatase inhibitor orthovanadate could restore ERK activation to a limited extent in some but not all v-Src-transformed cell lines. A similar repression of ERK activation was observed in v-Ras- and v-Raf-transformed cells. In addition, ERK activity was not constitutively elevated in exponentially growing cells transformed by v-Src, v-Ras, or v-Raf as compared with normal cells. These results establish that the ERK activation pathway is repressed in rodent fibroblasts stably transformed by viral oncoproteins that chronically stimulate receptor tyrosine kinase signaling pathways. Furthermore, our findings suggest that elevated ERK activity above basal levels is not required for maintaining cell transformation by these oncoproteins. Taken together, these results indicate that ERK signaling pathways are subject to negative feedback regulation upstream of ERK as a consequence of oncogenic transformation.

3T3 Cells↗

PubMed1997

Evoked facial nerve EMG and brainstem auditory evoked potential monitoring in cerebellopontine angle tumor resection.

BACKGROUND: The preservation of normal nerve function or identification of nerve route is critical in some surgeries of cerebellopontine angle tumors. Over the last 5 years, intraoperative facial nerve electromyogram (EMG) and brainstem auditory evoked potential (BAEP) were applied for evaluation of facial nerve integrity and brainstem function in patients while undergoing resection of cerebellopontine angle (CPA) tumor. This report represents the retrospective analysis of our results. METHODS: The inhalational anesthesia with 1-1.5% isoflurane in pure O2 was used. Muscle relaxation was maintained with continuous infusion of atracurium. The degree of muscle relaxation was aimed at a T4/T1 ratio of train-of-four response more than 20% of the adductus pollicis upon ulnar nerve stimulation at the wrist. In 236 patients suffering from CPA tumor without facial palsy, the EMG of the mentalis muscle ipisilateral to the tumor was obtained through stimulation of the facial nerve. The stimulation was applied with a nerve finder, which delivered an electrical stimulation of a single 2 mamp direct current. The EMG finding was compared with the clinical result. In 198 patients, BAEP was used to monitor the brainstem function during tumor resection. In case of intact hearing the BAEP was taken ipsilateral to the operation side and in case with total hearing loss contralateral BAEP to operation side was used. For BAEP stimulation, 90 db click sound stimulation with frequency of 11.26 Hz was applied to both ears. BAEP signals were obtained and recorded at the mastoid region of either side in reference to the vertex. The EMG and BAEP signals were recorded and saved to an evoked potential monitor. RESULTS: In facial nerve EMG monitoring, there were two false positive and no false negative tests. Except for the two false positive tests, the postoperative clinical results in the other cases were compatible with the intraoperative facial nerve EMG findings. In BAEP monitoring, there were twenty-eight positive tests. CONCLUSIONS: The low incidence of false negative test suggests that facial nerve EMG is valuable in detection of facial nerve function in CPA tumor resection. Intraoperative BAEP abnormality is possibly useful in identifying postoperative brainstem dysfunction.

Adult↗

PubMed1997

Constitutive activation of Stat3 in fibroblasts transformed by diverse oncoproteins and in breast carcinoma cells.

Signal transducers and activators of transcription (STATs) were originally identified as key components of signaling pathways involved in mediating responses to IFNs. Previous studies showed that the Src oncoprotein constitutively activates one STAT family member, Stat3. In this study, we investigated STAT activation in a panel of rodent fibroblast cell lines stably transformed by diverse viral oncoproteins. Using a temperature-sensitive mutant of v-Src, we determined that Stat3 is activated within 15 min of shift from nonpermissive to permissive temperature for cell transformation. This finding indicates that v-Src tyrosine kinase activity is required for Stat3 activation and suggests that Stat3 is proximal to signaling initiated by Src. In addition, Stat3 activation is induced by another nonreceptor tyrosine kinase, v-Fps; by polyoma virus middle T antigen, which activates Src family kinases; and by v-Sis, which acts as a ligand for the platelet-derived growth factor receptor. In contrast SV40 large T antigen, which transforms cells through different mechanisms, and the v-Ras and v-Raf oncoproteins, which lie in signaling pathways downstream of tyrosine kinases, do not activate Stat3. We did not detect significant activation of Stat1, Stat5, or Stat6 in fibroblasts transformed by the viral oncoproteins investigated. Moreover, Stat3 is activated in response to epidermal growth factor (EGF) but not heregulins in immortalized normal human breast epithelial cells. Because constitutive activation of c-Src and EGF receptor kinases is associated with the progression of breast cancer, we examined activation of STATs in human cell lines derived from breast carcinomas. We detected constitutive activation of Stat3 in five of nine breast carcinoma cell lines but not in normal breast epithelial cells. Furthermore, experiments with an EGF receptor-specific inhibitor indicated that the constitutive activation of Stat3 in these breast carcinoma cell lines is not necessarily dependent on signaling through the EGF receptor, although EGF stimulation further increases Stat3 activation. Taken together, our results demonstrate that selective activation of Stat3 is a common event during oncogenic transformation that directly or indirectly involves activation of specific tyrosine kinase signaling pathways.

3T3 Cells↗

PubMed1996

Heat shock and cytokines modulate the expression of adhesion molecules on different human gastric-cancer cell lines.

In order to understand the expression and modulation of adhesion molecules (AMs) on the surface of different gastric cancers, we studied 4 gastric-cancer cell lines including SC-M1, KATO-III, AGS and AZ-521. The expression of E-cadherin, integrins (beta1, beta2 and beta3), ICAMs (1 and 2), and CD11 (a, b and c) on the cells was detected by flow cytometry. We found that E-cadherin was only expressed on SC-M1 and KATO-III. CD29 (beta1 integrin) could be found in cells of all 4 lines. CD54 (ICAM- 1) could not be detected in AZ-521. In contrast, CD18 (beta2 integrin), CD61 (beta3 integrin), ICAM-2, CD11a, CD11b and CD11c were all absent from these cells. Heat-shock treatment (42.5 degrees C, 60 min) enhanced the expression of E-cadherin, CD29 and CD54 on SC-M1, and of CD29 on AGS. In addition, TNF-alpha (50U/ml) and IL-1beta (10U/ml) modulated the expression of these AMs, like heat-shock treatment. The increment of these adhesion molecules caused by heat shock, TNF-alpha and IL-1beta stimulation on SC-M1 was also confirmed by Western blot analysis. Functionally, these treatments increased the binding between normal human mononuclear cells and SC-Ml cells. The heat-shock treatment could induce a significant amount of TNF-alpha and IL-1beta release from SC-M1 and KATO-III, but seemed irrelevant to the expression of AMs. These results suggest that limited adhesion molecules were expressed on the surface of different gastric cancer cells. Heat shock, IL-1beta and TNF-alpha may selectively modulate the expression of these 3 molecules on some of the cells, and this is probably related to their antitumor effect.

Antigens, CD↗

PubMed1996

Modulation of the transcriptional activity of thyroid hormone receptors by the tumor suppressor p53.

Thyroid hormone nuclear receptors (TRs) are ligand-dependent transcriptional factors that regulate growth, differentiation, and development. The molecular mechanisms by which TRs mediate these effects are unclear. One prevailing hypothesis suggests that TRs may cooperate with other transcriptional factors to mediate their biological effects. In this study, we tested this hypothesis by examining whether the activity of TRs is modulated by the tumor suppressor p53. p53 is a nuclear protein that regulates gene expression via sequence-specific DNA binding and/or direct protein-protein interaction. We found that the human TR subtype beta 1 (h-TR beta 1) physically interacted with p53 via its DNA binding domain. As a result of this physical interaction, binding of h-TR beta 1 to its hormone response elements either as homodimer or as a heterodimer with the retinoic X receptor was inhibited by p53 in a concentration-dependent manner. In transfected cells, wild-type p53 repressed the hormone-dependent transcriptional activation of h-TR beta 1. In contrast, mutant p53 either had no effect or activated the transcriptional activity of h-TR beta 1 depending on the type of hormone response elements. These results indicate the gene regulating activity of TRs was modulated by p53, suggesting that the cross talk between these two transcriptional factors may play an important role in the biology of normal and cancer cells.

Animals↗

PubMed1996

Deterioration of cutaneous microcirculatory status and its clinical correlation in tetralogy of Fallot.

The purpose of this study was to evaluate the hemodynamic deterioration in cutaneous microcirculation and its clinical correlation in patients with tetralogy of Fallot (TF). Laser Doppler flowmetry and capillary microscopy were used to assess thermoregulatory and nutritional microcirculation, respectively. A significant increase in blood flow in thermoregulatory vessels was noticed only in TF patients with hemoglobin (Hb) levels under 19 g/dl. In patients with Hb levels above 19 g/dl, the blood flow declined into the normal range. This result indicated an extreme decrease of blood flow velocity in the thermoregulatory vessels in patients with Hb concentration higher than 19 g/dl. All TF patients with Hb concentrations higher than 19 g/dl revealed Maricq's type III capillaries. Type III capillaries revealed a significant retardation of capillary blood cell velocity (CBV). There was a reciprocal relationship between CBV and hematocrit (Hct). All the responses of the cutaneous microcirculation revealed a good correlation with the clinical severity of TF. All patients with type III capillaries (with Hb concentrations higher than 19 g/dl or Hct level higher than 60%) indicated an advanced disease progression. Laser Doppler flowmetry and capillary microscopy provide a sensitive noninvasive approach for the evaluation of the hemodynamic disturbances in TF and conditions resulting from long-term hypoxia.

Adolescent↗