The effect of hyperbaric oxygen on medial collateral ligament healing in a rat model

Hyperbaric oxygen has been shown to promote healing in bone and some soft tissues. This study was undertaken to determine its effect on ligamentous healing. Forty-eight Sprague-Dawley rats underwent a standardized surgical laceration of the right (divided) medial collateral ligament, whereas the left (undivided) medial collateral ligament was not surgically lacerated. A control group of 24 rats recovered without intervention. An experimental group consisting of the other 24 rats was exposed to hyperbaric oxygen at 2.8 atmospheres for 1.5 hours a day for 5 days after the surgery. Six rats from each group were euthanized at 2, 4, 6, and 8 weeks. The stiffness and final force to failure were recorded for the divided and undivided medial collateral ligaments. At 4 weeks, a statistically greater force was required to cause failure of the previously divided ligaments that had been exposed to hyperbaric oxygen than those that had not. The stiffness and force to cause failure of previously divided ligaments were statistically greater at 4 weeks than at 2 weeks, whether or not hyperbaric oxygen was used. No additional statistical increases in stiffness or force were observed at 6 weeks.     

Clear cell sarcoma of kidney in an adolescent and in young adults: a report of four cases with ultrastructural, immunohistochemical, and DNA flow cytometric analysis

Clear cell sarcoma of the kidney is a distinct, highly malignant pediatric neoplasm. Its occurrence in adults is extremely rare and the subject of isolated case reports. We present a series of four cases (three males and one female) identified in an adolescent and in young adults (16, 18, 20, and 25 years) with flank mass (three cases), hematuria (two cases), flank pain (two cases), and hypertension (one case). Three patients had stage III disease and one had stage I disease (National Wilms' Tumor Study staging system). All tumors had predominantly or exclusively the classic histology of a monotonous proliferation of uniform small round cells with evenly distributed fine chromatin, although focal microcyst formation (two cases) and spindled architecture (one case) (variant patterns) were also noted. Therapy in all cases consisted of surgery and chemotherapy with or without radiation. Follow-up data (29-202 months) showed distant metastases in all four cases, including the lung (four cases), bone (two cases), and the liver (two cases). Three patients died of disease at 29, 59, and 63 months (mean, 50.3 months), and one patient is alive with no evidence of disease at 202 months. Ultrastructural features included scattered primitive junctions, short and irregular cytoplasmic extensions, and scant to a moderate amount of mitochondria. Immunohistochemical study (three cases) showed immunoreactivity with vimentin (two cases) and no reaction with cytokeratin, epithelial membrane antigen, S-100 protein, or desmin. Flow cytometric analysis showed diploid DNA content in three primary tumors and tetraploidy in one metastatic tumor. The proliferative activity (S-phase fraction) was low to intermediate (mean, 9.8%). Our data suggest that clear cell sarcoma of the kidney in the young adult age group resembles its pediatric counterpart in ultrastructural and immunohistochemical characteristics, proclivity for skeletal and visceral metastasis, DNA diploid status with relatively low S-phase, and aggressive clinical course. Clear cell sarcoma of the kidney in adult patients, although rare, must be differentiated from sarcomatoid carcinoma, sarcomas, and round cell tumors because of its unique characteristics in comparison to other renal neoplasms.     

A single hydrophobic residue confers barbiturate sensitivity to gamma-aminobutyric acid type C receptor

Barbiturate sensitivity was imparted to the human rho1 homooligomeric gamma-aminobutyric acid (GABA) receptor channel by mutation of a tryptophan residue at position 328 (Trp328), which is located within the third transmembrane domain. Substitutions of Trp328 with a spectrum of amino acids revealed that nearly all hydrophobic residues produced receptor channels that were both directly activated and modulated by pentobarbital with similar sensitivities. Previous studies with ligand-gated ion channels (including GABA) have demonstrated that even conservative amino acid substitution within the agonist-dependent activation domain (N-terminal extracellular domain) can markedly impair agonist sensitivity. Thus, the lack of significant variation in pentobarbital sensitivity among the Trp328 mutants attests to an intrinsic difference between pentobarbital- and the GABA-dependent activation domain. Compared with the heterooligomeric alphabetagamma receptor channel, the mode of modulation for homooligomeric Trp328 mutants by pentobarbital was more dependent on the GABA concentration, yielding potentiation only at low concentrations of GABA (fractions of their respective EC50 values), yet causing inhibition at higher concentrations. Agonist-related studies have also demonstrated that residue 328 plays an important role in agonist-dependent activation, suggesting a functional interconnection between the GABA and pentobarbital activation domains.     

Expression of adhesion molecules in B-cell chronic lymphocytic leukaemia: an analysis in lymphoid compartments--peripheral blood, bone marrow and lymph node

The trafficking or homing of different lymphoid subsets to particular microenvironment is mediated by specific cell adhesion molecules (CAMs) expressed on lymphocytes and endothelial cells. B-cell chronic lymphocytic leukaemia (B-CLL) or Non-Hodgkin's lymphoma of small lymphocytic, B-cell type are monoclonal expansions of mature lymphocytes. The relative distribution of the tumor lymphocytes among various lymphoid compartments vary from patient to patient. Very few studies underlying this issue are available. To this effect, we have analysed the expression of LFA-1; VLA-4, ICAM-1; CD44H and CD44v6 (haematopoietic and variant form respectively) on freshly isolated lymphocytes obtained from bone marrow (BM), peripheral blood (PB) and lymph node (LN) by flow cytometry. Overall, we find strong expression of CD44H, low to moderate expression of LFA-1, negative to low expression of VLA-4 and lack of expression of CD44v6. ICAM-1 expression was observed only in patients with prominent lymphadenopathy. Higher expression of CD44H in PB lymphoid cells relative to that of BM lymphoid cells correlated with higher PB lymphocytosis (p < 0.001). Proliferating cell nuclear antigen expression in LN sections correlated inversely with VLA-4 expression on BM and PB lymphoid cells (p < 0.05). There was no significant correlation between expression of CAMs and bcl-2 protein.     

Brainstem maturation after antenatal steroids exposure in premature infants as evaluated by auditory brainstem-evoked response.

OBJECTIVE: Antenatal steroids result in fetal lung maturation, but may retard brain development. Auditory brainstem-evoked response (ABR) is a noninvasive assessment of brainstem maturation. The objective of this study was to determine if antenatal steroids affect brainstem maturation in infants 相似文献   

Intravesical adipose tissue: a quantitative study of its presence and location with implications for therapy and prognosis

Accurate pathologic staging of carcinomas of the urinary bladder involves assessment of invasion by the tumor into the bladder wall and beyond into perivesical soft tissue. The presence of tumor within perivesical soft tissue implies pathologic stage pT3 (AJCC/UICC system, 1997). In traditional textbooks of histology, anatomy, pathology, and in the literature, other than a single case report and a brief reference in another paper, there is no information on the presence of adipose tissue in the lamina propria or muscularis propria of the urinary bladder. Nine hundred forty-three sections from 139 cystectomy specimens were evaluated for the presence, location, and quantity of adipose tissue within the lamina propria and muscularis propria. The histology of the perivesical soft tissues and the nature of its delineation from muscularis propria were also analyzed. Adipose tissue was seen within the lamina propria in 53% (74 of 139) of cystectomies and in 17.6% (166 of 943) of the examined sections. It was located predominantly in the deep lamina propria (at or below the muscularis mucosae) in 81.1% (60 of 74) of the cystectomies and in 91% (151 of 166) of the sections. Within the lamina propria it was predominantly seen as small localized aggregates in 92% (153 of 166) of sections. All cases showed adipose tissue within the muscularis propria. Adipose tissue was identified within the superficial (inner) muscularis propria in 54% (512 of 943) of sections and was predominantly in small aggregates in 80.5% (412 of 512) of sections. It was in moderate to abundant quantities within the deep (outer) muscularis propria in 60.7% (572 of 943) of sections. The perivesical soft tissue was almost exclusively composed of adipose tissue with variable vascularity. Delineation of the perivesical adipose tissue from the deep (outer) muscularis propria was typically indistinct because muscle bundles of the latter haphazardly merged with the perivesical adipose tissue. Based on these findings, we conclude that adipose tissue is frequently present in the lamina propria and muscularis propria of the urinary bladder wall, and is usually scant in the former location and frequently abundant in the latter. Awareness of the high frequency of adipose tissue within the urinary bladder wall has prognostic and therapeutic implications. In transurethral resection of bladder tumor (TURBT) specimens, misinterpretation of tumor infiltrating adipose tissue within lamina propria (pT1) as perivesical soft tissue involvement (pT3) may potentially result in unwarranted aggressive management. Substaging of muscle invasive tumors should be performed in cystectomy specimens only, because the junction of muscularis propria and the perivesical adipose tissue is typically ill-defined. Muscularis propria adipose tissue in TURBT specimens may be erroneously assumed to be perivesical adipose tissue, potentially leading to overstaging of the primary tumor.     

Comparative mouse skin tumorigenicity and induction of Ha-ras mutations by bay region diol epoxides of 5-methylchrysene and 5,6- dimethylchrysene

We compared the tumor-initiating activities toward mouse skin of two structurally related polycyclic aromatic hydrocarbon diol epoxides: racemic anti-1,2,3,4-tetrahydro-5,6-dimethylchrysene-1,2-diol-3,4- epoxide (5,6-diMeCDE) and racemic anti-1,2,3,4-tetrahydro-5- methylchrysene-1,2-diol-3,4-epoxide (5-MeCDE). Tumors induced by these diol epoxides were analysed for mutations in the Ha-ras gene. 5,6- diMeCDE is derived from the non-planar parent compound 5,6- dimethylchrysene, and reacts to approximately equal extents with dA and dG in DNA, whereas 5-MeCDE is derived from a nearly planar parent compound, 5-methylchrysene, and reacts mainly with dG in DNA. 5,6- diMeCDE, at initiating doses of 33, 100 or 400 nmol per mouse, induced 1.2, 2.2 and 6.2 skin tumors per mouse, respectively. It was significantly less tumorigenic than 5-MeCDE which induced 3.1, 7.5 and 9.1 skin tumors per mouse at the same doses. Tumors induced by 5,6- diMeCDE had a large number of CAA-->CTA mutations in codon 61 of the Ha- ras gene: 50, 55 and 75% of the tumors analysed had this mutation at the 33, 100 and 400 nmol doses. No mutations were found in codons 12 and 13 in the tumors induced by 5,6-diMeCDE. In contrast, CAA-->CTA mutations in codon 61 were rarely seen in tumors induced by 5-MeCDE. At the highest dose of 5-MeCDE, 20% of the tumors analysed had mutations at G of codons 12 and 13. The results of this comparative study support the hypothesis that mutations in the Ha-ras gene in mouse skin tumors induced by PAH diol epoxides occur as a result of their direct reaction with the gene. However, pathways other than the commonly observed Ha- ras codon 61 mutations are clearly important in mouse skin tumorigenesis by these diol epoxides.      

Erythropoietin and erythropoietin receptor expression in head and neck cancer: relationship to tumor hypoxia.

PURPOSE: Erythropoietin, an oxygen-regulated glycoprotein hormone, is a hematopoietic cytokine that stimulates erythropoiesis by binding to its cellular receptor [erythropoietin receptor (EPOR)]. The recombinant form of human erythropoietin is used to prevent or treat anemia in cancer patients. However, in a recent randomized, placebo-controlled trial involving patients receiving curative radiotherapy for squamous cell carcinoma of the head and neck, erythropoietin treatment was associated with poorer locoregional progression-free survival. The purpose of our study was to determine whether EPOR and its ligand erythropoietin are expressed in primary head and neck cancer. We also investigated the hypothesis that erythropoietin expression in malignant cells may be associated with the presence of tumor hypoxia, an important factor involved in resistance to radiation treatment, tumor aggressiveness, and poor prognosis. EXPERIMENTAL DESIGN: Twenty-one patients received an i.v. infusion of the hypoxia marker pimonidazole hydrochloride before multiple tumor biopsies. Contiguous sections from 74 biopsies were analyzed by immunohistochemistry for EPOR and erythropoietin expression and pimonidazole binding. RESULTS: EPOR expression was present in tumor cells in 97% of the biopsies. Coexpression of erythropoietin was observed in 90% of biopsies. Erythropoietin and pimonidazole adduct staining did not always colocalize within tumors, but there was a significant positive correlation between levels of microregional erythropoietin expression and pimonidazole binding. CONCLUSIONS: The coexpression of erythropoietin and EPOR in tumor cells suggests that erythropoietin may potentially function as an autocrine or paracrine factor in head and neck cancer. The expression of the hypoxia-inducible protein erythropoietin in tumor cells correlates with levels of tumor hypoxia.     

Association of dry eye disease with smoking: A systematic review and meta-analysis

There is conflicting evidence for the association between smoking and dry eye disease (DED). We conducted a meta-analysis to determine the true relationship between smoking and DED. A systematic literature search was performed using electronic databases, including PubMed, Embase and Cochrane Library, till August 2021 to identify observational studies with data on smoking as risk factor of DED. Quality assessment of the included studies was conducted using Joanna Briggs Institute (JBI) critical appraisal checklists. The random-effects model was used to calculate the pooled odds ratio (OR). Heterogeneity was evaluated by Cochrane Q and I² index; in addition, subgroup, sensitivity, and meta-regression analyses were performed. Publication bias was assessed using funnel plot and Egger’s regression test. A total of 22 studies (4 cohort and 18 cross-sectional studies) with 160,217 subjects met the inclusion criteria and were included in this meta-analysis. There is no statistically significant relationship between current smokers (OR_adjusted = 1.14; 95% CI: 0.95–1.36; P = 0.15; I² = 84%) and former smokers (OR_adjusted = 1.06; 95% CI: 0.93–1.20; P = 0.38; I² = 26.7%) for the risk of DED. The results remained consistent across various subgroups. No risk of publication bias was detected by funnel plot and Eggers’s test (P > 0.05). No source of heterogeneity was observed in the meta-regression analysis. Our meta-analysis suggest current or former smoking may not be involved in the risk of dry eye disease. Further studies to understand the mechanism of interaction between current smokers and formers smokers with DED are recommended.     

Size-fractionated heparins have differential effects on human neutrophil function in vitro

BACKGROUND AND PURPOSE: Heparin is known to possess a range of activities, other than effects on blood coagulation, many of which are anti-inflammatory. Effects with potential anti-inflammatory applications include the inhibition of elastase release from neutrophils, as well as the adhesion of these cells to vascular endothelium. In the present study we aimed to investigate whether fractionation of heparin may yield molecules with enhanced or specific effects on human neutrophil function. EXPERIMENTAL APPROACH: Fractions of defined molecular size were obtained from heparin by different methods and assessed for their effects on elastase release induced by formyl Met-Leu-Phe (fMLP), from neutrophils, in some cases following the priming of these cells with tumour necrosis factor-alpha (TNF-alpha). Effects of the fractions on neutrophil adhesion to interleukin-1beta (IL-beta)-stimulated human umbilical vein endothelial cells (HUVECs) were also examined. KEY RESULTS: Elastase release was inhibited by very low molecular weight fractions of heparin, with an apparent minimum chain length of 10 saccharides required for full effect. In contrast, neutrophil-endothelial adhesion was unaffected by these fractionated heparins, suggesting that certain non-anticoagulant actions of heparin may be lost by such an approach. CONCLUSIONS AND IMPLICATIONS: These data suggest that an optimum chain length of heparin possibly exists for certain non-anticoagulant actions of heparin, which may prove to be useful in the design of novel drugs with specific anti-inflammatory actions.