scholarly journals Testicular immune cells and vasculature in Klinefelter syndrome from childhood up to adulthood

2020 ◽  
Vol 35 (8) ◽  
pp. 1753-1764
Author(s):  
Margo Willems ◽  
Veerle Vloeberghs ◽  
Inge Gies ◽  
Jean De Schepper ◽  
Herman Tournaye ◽  
...  
Keyword(s):  
Mast Cells ◽  
Blood Vessel ◽  
Immune Cells ◽  
Testicular Tissue ◽  
Vessel Density ◽  
Blood Vessel Density ◽  
Significant Difference ◽  
Secretory Products ◽  
And Control ◽  
Control Samples

Abstract STUDY QUESTION Is the distribution of immune cells and the testicular vasculature altered in testicular biopsies from patients with Klinefelter syndrome (KS)? SUMMARY ANSWER Increased numbers of macrophages and mast cells, an increased expression of decorin and an increased blood vessel density were found in KS samples compared to controls. WHAT IS KNOWN ALREADY Most KS patients are infertile due to an early germ cell loss. From puberty onwards, testicular fibrosis can be detected. How this fibrotic process is initiated remains unknown. STUDY DESIGN, SIZE, DURATION In this study, the number of macrophages, mast cells and their secretory products were evaluated in KS, Sertoli cell only (SCO) and control patient samples. The association between immune cell numbers and level of fibrosis in KS tissue was examined. In addition, the vascularization within these testicular tissue biopsies was studied. For immunohistochemical evaluation, KS patients at different stages of testicular development were included: prepubertal (aged 4–7 years; n = 4), peripubertal (aged 11–17 years; n = 21) and adult (aged >18 years; n = 37) patients. In addition, testicular tissue biopsies of adult SCO (n = 33) and control samples for the three KS age groups (prepubertal n = 9; peripubertal n = 5; adult n = 25) were analysed. Gene expression analysis was performed on adult testicular tissue from KS (n = 5), SCO (n = 5) and control (n = 5) patients. PARTICIPANTS/MATERIALS, SETTING, METHODS Adult (>18 years) KS, SCO and control testicular tissue biopsies were obtained during a testicular sperm extraction procedure. KS peripubertal (11–18 years), prepubertal (<11 years) and age-matched control biopsies were obtained from the biobank of the university hospital. Immunohistochemistry was used to determine the tubular structure (H/PAS), the number of spermatogonia (MAGE-A4), macrophages (CD68) and mast cells (tryptase) and the blood vessel density (Von Willebrand factor). In addition, quantitative real-time polymerase chain reaction was used to determine the expression of secretory products of macrophages and mast cells (tryptase, tumour necrosis factor alpha and decorin). MAIN RESULTS AND THE ROLE OF CHANCE A significant increase in the number of macrophages (P < 0.0001) and mast cells (P = 0.0008) was found in the peritubular compartment of testes of adult KS patients compared to control samples. However, no association between the number of immune cells and the degree of fibrosis was observed. In adult SCO samples, a significant increase was seen for peritubular macrophage (P < 0.0001) and mast cell (P < 0.0001) numbers compared to control samples. In the interstitial compartment, a significant increase in mast cell number was found in adult SCO samples compared to KS (P < 0.0001) and control (P < 0.0001) tissue. A significant difference (P = 0.0431) in decorin expression could be detected in adult KS compared to control patients. Decorin expression was mostly seen in the walls of the seminiferous tubules. When comparing the vascularization between KS patients and age-matched controls, a significant increase (P = 0.0081) in blood vessel density could be observed only in prepubertal KS testicular tissue. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION As controls for this study, testicular tissue biopsies of men who underwent a vasectomy reversal or orchiectomy were used, but these men may not represent fertile controls. In addition, a high variability in immune cell numbers, secretory products expression and number of blood vessels could be observed amongst all patient samples. WIDER IMPLICATIONS OF THE FINDINGS Increased numbers of macrophages and mast cells have previously been described in non-KS infertile men. Our results show that these increased numbers can also be detected in KS testicular tissue. However, no association between the number of macrophages or mast cells and the degree of fibrosis in KS samples could be detected. Decorin has previously been described in relation to fibrosis, but it has not yet been associated with testicular fibrosis in KS. Our results suggest a role for this proteoglycan in the fibrotic process since an increased expression was observed in adult KS tissue compared to controls. Impaired vascularization in KS men was suggested to be responsible for the KS-related disturbed hormone levels. Our results show a significant difference in blood vessel density, especially for the smallest blood vessels, between prepubertal KS samples and age-matched controls. This is the first study to report differences between KS and control testicular tissue at prepubertal age. STUDY FUNDING/COMPETING INTEREST(S) The project was funded by grants from the Vrije Universiteit Brussel (E.G.) and the scientific Fund Willy Gepts from the UZ Brussel (D.V.S.). D.V.S. is a post-doctoral fellow of the Fonds voor Wetenschappelijk Onderzoek (FWO; 12M2819N). No conflict of interest is declared for this research project.

505. THE ROLE OF Adamts1 IN BREAST CANCER PROGRESSION AND METASTASIS

2009 ◽  
Vol 21 (9) ◽  
pp. 105
Author(s):  
I. A. Tan ◽  
K. M. Frewin ◽  
C. Ricciardelli ◽  
D. L. Russell
Keyword(s):  
Breast Cancer ◽  
Blood Vessel ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Progression ◽  
Vessel Density ◽  
Blood Vessel Density ◽  
Immunohistochemical Markers ◽  
Significant Difference

The extracellular protease Adamts1 is a vital enzyme involved in normal development and has been associated with various processes of extracellular matrix (ECM) remodelling including ovulation and pathologies exhibiting disrupted ECM. In the PyMT-MMTV mouse mammary cancer model we have demonstrated reduced tumour growth and pulmonary metastasis incidence in Adamts1–/– mice. Furthermore, benign DCIS lesions of the mammary gland were significantly more common in Adamts1–/– mice. To better understand the mechanisms surrounding Adamts1 mediated progression from DCIS to invasive cancer we next investigated proliferation, apoptosis, blood vessel density and/or extracellular remodelling. Morphometric comparisons were performed using immunohistochemical markers of proliferation (Ki67) and apoptosis (active caspase3) as well as vasculature (CD34), and known Adamts1 proteolytic target, versican in wildtype and Adamts1-/-PyMT tumours. Our analysis revealed that no significant difference in proliferation between the two genotypes, but Adamts1–/– had increased apoptosis compared with Adamts1+/+ tumours. Contrary to previous reports suggesting Adamts1 is antiangiogenic, no significant difference was found in blood vessel density between Adamts1–/– compared with Adamts1+/+ tumours. Interestingly, versican abundance in peritumoural stroma was lower in Adamts1–/– tumours. This latter finding may provide an explanation for the reduced metastasis incidence found after Adamts1gene inactivation, as many previous studies have associated peritumoral versican abundance to metastasic progression. Our findings increase the understanding of mechanisms whereby Adamts1 promotes breast cancer metastasis by showing its role in increasing cell survival, as well as modulating the stromal ECM environment through which it may promote invasion and metastasis. The involvement of Adamts1 in breast cancer progression presents this protease as a potential novel target for reducing metastasis incidence.

scholarly journals Phosphorylation of pericyte FAK-Y861 affects tumour cell apoptosis and tumour blood vessel regression

Angiogenesis ◽  
2021 ◽  
Author(s):  
Delphine M. Lees ◽  
Louise E. Reynolds ◽  
Ana Rita Pedrosa ◽  
Marina Roy-Luzarraga ◽  
Kairbaan M. Hodivala-Dilke
Keyword(s):  
Blood Vessel ◽  
Tumour Growth ◽  
Vascular Endothelial Cell ◽  
Vessel Density ◽  
In Vivo Studies ◽  
Blood Vessel Density ◽  
Tumour Vessel ◽  
Vessel Regression ◽  
Tumour Blood

AbstractFocal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is overexpressed in many cancer types and in vivo studies have shown that vascular endothelial cell FAK expression and FAK-phosphorylation at tyrosine (Y) 397, and subsequently FAK-Y861, are important in tumour angiogenesis. Pericytes also play a vital role in regulating tumour blood vessel stabilisation, but the specific involvement of pericyte FAK-Y397 and FAK-Y861 phosphorylation in tumour blood vessels is unknown. Using PdgfrβCre + ;FAKWT/WT, PdgfrβCre + ;FAKY397F/Y397F and PdgfrβCre + ;FAKY861F/Y861F mice, our data demonstrate that tumour growth, tumour blood vessel density, blood vessel perfusion and pericyte coverage were affected only in late stage tumours in PdgfrβCre + ;FAKY861F/Y861F but not PdgfrβCre + ;FAKY397F/Y397F mice. Further examination indicates a dual role for pericyte FAK-Y861 phosphorylation in the regulation of tumour vessel regression and also in the control of pericyte derived signals that influence apoptosis in cancer cells. Overall this study identifies the role of pericyte FAK-Y861 in the regulation of tumour vessel regression and tumour growth control and that non-phosphorylatable FAK-Y861F in pericytes reduces tumour growth and blood vessel density.

scholarly journals Increased Skin Inflammation and Blood Vessel Density in Human and Experimental Diabetes

2013 ◽  
Vol 12 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Ana Tellechea ◽  
Antonios Kafanas ◽  
Ermelindo C. Leal ◽  
Francesco Tecilazich ◽  
Sarada Kuchibhotla ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Blood Vessels ◽  
Experimental Diabetes ◽  
Human Subjects ◽  
Inflammatory Cells ◽  
Skin Inflammation ◽  
Vessel Density ◽  
Impaired Wound Healing ◽  
Blood Vessel Density ◽  
Skin Blood Vessels

Systemic inflammation is associated with impaired wound healing in diabetes mellitus (DM) patients. Using immunohistochemistry techniques, the authors investigated changes in skin inflammation and skin blood vessels in human and experimental diabetes. Comparing to the non-DM human subjects, the total number of inflammatory cells per biopsy and the number of inflammatory cells around blood vessels, a strong indication of inflammation, were higher in DM subjects irrespective of their risk for developing diabetic foot ulcer. Inflammatory cell infiltration was robustly increased in all DM animal models compared with their non-DM controls. The number and density of blood vessels and CD31 positive proliferating endothelial cells around preexisting skin vessels was also higher in the DM patients. However, there were no differences in the skin blood flow between the non-DM and DM subjects. The number of skin blood vessels was also increased in the DM animals; however, these differences were less obvious than the ones observed for inflammatory cells. We conclude that skin inflammation and skin blood vessel density is increased in diabetic human subjects and in rodent and rabbit models of diabetes.

Prognostic value of blood vessel density in ischaemic stroke

The Lancet ◽  
1993 ◽  
Vol 342 (8873) ◽  
pp. 742 ◽  
Author(s):  
J. Krupinski ◽  
J. Kaluza ◽  
P. Kumar ◽  
M. Wang ◽  
S. Kumar
Keyword(s):  
Blood Vessel ◽  
Ischaemic Stroke ◽  
Prognostic Value ◽  
Vessel Density ◽  
Blood Vessel Density

OCT Angiography of the Central Macular Capillary Network in Glaucoma Patients and Healthy Controls

2018 ◽  
Vol 235 (04) ◽  
pp. 436-444
Author(s):  
Olena Müller ◽  
Margarita G. Todorova ◽  
Torsten Schlote
Keyword(s):  
Optical Coherence Tomography ◽  
Structural Changes ◽  
Ganglion Cells ◽  
Retinal Nerve Fibre Layer ◽  
Vessel Density ◽  
Healthy Controls ◽  
Optical Coherence ◽  
Significant Difference ◽  
Nerve Fibre Layer ◽  
And Control

Abstract Purpose We aimed to investigate central macular microvasculature by optical coherence tomography angiography (OCTA) and to analyse its relation to alterations in classical parameters of optical coherence tomography (OCT) in glaucoma patients. Methods Using OCTA (Avanti incl. AngioVue; Optovue, Inc., Fremont, CA), the superficial flow (SF) and the superficial non-flow (SNF) area of the macula, as well as the S-ETDRS (based on Early Treatment Diabetic Retinopathy charts). and S-grid vessel density (zones 1 – 9) of the macula, were evaluated in 27 glaucoma patients (49 eyes) and compared to those of 27 age-matched healthy controls (50 eyes; p = 0.253). The interactions between OCTA parameters representing macular microvasculature and classical OCT measurements of the circumpapillary retinal nerve fibre layer (RNFL) and macular ganglion cells (mGCC) were analysed within groups (linear mixed-effects model). Results SF, SNF, and S-ETDRS vessel density exhibited no significant difference between the glaucoma and control groups (all p ≥ 0.158). However, within the glaucoma group, decreased RNFL and mGCC thickness correlated significantly with decreased S-ETDRS density (zones 1; 2 – 9, p ≤ 0.033). The same held true for the interactions between the RNFL and mGCC thickness with S-grid density (zones 1 – 3; 6 – 9; p ≤ 0.033). For perimetric glaucoma patients, subgroup analyses demonstrated significantly reduced density maps of superficial foveal flow as well as significant interactions between OCT and OCTA parameters; this was not the case within the preperimetric group. Conclusions Even if the central macular microvasculature, as measured by SF and SNF, is found preserved in glaucoma, the strong positive relation between the central microvascular and structural changes in OCTA and OCT indicates that there are alterations in central macular microvasculature in subclinical glaucoma.

THE APPLICATION OF PLASTIC CONTAINERS FOR PACKING AND PASTEURIZING MEAT OF THE BLUE CRAB (CALLINECTES SAPIDUS)1

1966 ◽  
Vol 29 (7) ◽  
pp. 218-221 ◽  
Author(s):  
C. W. Flynn ◽  
M. C. Tatro
Keyword(s):  
Blue Crab ◽  
Callinectes Sapidus ◽  
Bacteriological Examination ◽  
Flavor Evaluation ◽  
Significant Difference ◽  
Product Protection ◽  
Crab Meat ◽  
And Control ◽  
Plastic Containers ◽  
Control Samples

Summary Sixteen-ounce portions of regular grade crab meat were packed and pasteurized in hermetically sealed rigid polypropylene “Indeplas” 307 × 400 containers. Meat from the metal and plastic containers was evaluated periodically for six months. The plastic containers gave overall product protection equal to the metal cans. Some brittleness was experienced with the plastic containers when handled roughly at refrigerated temperatures. Appearance and flavor evaluation of experimental and control samples within each treatment resulted in no significant difference until approaching four months storage. At four months and thereafter, the meat from the plastic containers appeared whiter and imparted a sweeter, more natural flavor than the control samples packed in metal containers. A preference was observed for appearance and flavor of meat processed at 185 F over that processed at 190 F. Above 190 F the meat exhibited a greyish cast and a slightly cooked flavor. Texture evaluation data indicated no significant change throughout the storage testing. Bacteriological examination indicated that the contents in both containers should be processed 110 min at 185 F for adequate pasteurization. The metal containers, due to their increased diameter, exhibited a slightly slower come-up time.

Ribosomal Protein S24 Gene Is Mutated in Diamond-Blackfan Anemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 181-181 ◽  
Author(s):  
Hanna Gazda ◽  
Agnieszka Grabowska ◽  
Lilia Long ◽  
Elzbieta Latawiec ◽  
Hal Schneider ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Cell Lines ◽  
Nonsense Mutation ◽  
Lymphoblastoid Cell Lines ◽  
Rt Pcr ◽  
Exon 2 ◽  
Diamond Blackfan Anemia ◽  
Significant Difference ◽  
And Control ◽  
Control Samples

Abstract Diamond-Blackfan anemia (DBA) is a congenital red cell aplasia with marked clinical heterogeneity, an increased risk of malignancy and mutations in ribosomal protein (RP) S19 in 25% of probands. To identify other gene(s) mutated in DBA and investigate their expression and function, we performed a genome-wide screen using a 10,000 single nucleotide polymorphism mapping set (Affymetrix) on a large family comprising 10 informative meioses. We found linkage of the DBA phenotype to regions on chromosome 8q, 10 and 6. The RP gene RPS24, is located in the linked region on chromosome 10; we sequenced exons, intron-exon boundaries and the promoter regions in this family, and found a nonsense mutation (316C>T) in exon 4 of RPS24 in five affected individuals, and a wild type sequence in five unaffected family members. This mutation causes the change of Gln106STOP and is predicted to result in formation of a truncated RPS24 protein. Subsequently, we sequenced DNA from 215 unrelated DBA probands, 30 with RPS19 mutations and 185 without. We found another nonsense mutation in exon 2 in a sporadic case, and a splice site deletion resulting in skipped exon 2 in another proband and in his father; over 200 control individuals did not have any of the above sequence changes, indicating that they are pathogenic mutations. To explore the normal role of RPS24 and consider how its dysfunction might result in DBA we performed real time RT-PCR (rt-PCR) and western blotting experiments on 20 normal human tissues and on lymphoblastoid cell lines from diseased and control individuals. Interestingly, rt-PCR of total human RPS24 and RPS19 mRNA revealed a tissue-specific variation in expression level. We found co-ordinate expression of both genes in the majority of studied tissues. Lymphoblastoid cell lines from both probands with nonsense mutations showed a reduced level of RPS24 mRNA, suggesting degradation of mutated transcripts due to nonsense mediated decay, while the RPS19 mRNA level in these patients was normal or elevated. Western blot experiments revealed a reduction of RPS24 protein in lymphoblastoid cell lines from all three mutated probands compared to control samples. Interestingly, co-ordinate expression of RPS24 and RPS19 protein was found in these patients as well as in other patients with RPS19 mutations or without any mutations, suggesting co-regulation of RP expression. To determine whether recruitment of mRNA to polysomes was impaired in DBA patients, we separated lymphoblast cell line lysates from nine diseased and four control individuals on sucrose gradients. We did not detect any significant difference in the RNA ratio of polysome-bound/free ribosomal subunits between diseased and control samples (p<0.3). It is likely that lymphoblasts, which are not defective in DBA, have sufficient ribosomes to mask an abnormality in translation. In summary, our results suggest that in addition to RPS24 and RPS19, which are mutated in ~ 27% of index cases, other DBA genes are also RP genes or genes involved in ribosome biogenesis or translation, and reinforce the notion that DBA is a ribosomal disease. This study opens new avenues for studying and understanding the pathogenesis of DBA.

scholarly journals Effect of 1-MCP, ethylene absorber and ozone on melon quality during storage

2018 ◽  
Vol 14 (s1) ◽  
pp. 101-110
Author(s):  
Lien Phuong Le Nguyen ◽  
Vivien Horváth ◽  
Mai Sao Dam ◽  
Géza Hitka ◽  
Tamás Zsom ◽  
...  
Keyword(s):  
Disease Severity ◽  
Cold Storage ◽  
Ethylene Production ◽  
Chilling Injury ◽  
Ozone Treatment ◽  
Surface Color ◽  
Respiration Rates ◽  
Significant Difference ◽  
And Control ◽  
Control Samples

This work was aimed to investigate the effect of 1-methylcyclopropene (1-MCP), ethylene absorber (EA), ozone alone or in combination on melon quality during storage. Ethylene production, respiration rates, acoustic firmness, surface color, chilling injury, and disease severity of melon were determined. 1-MCP treated fruits and non 1-MCP treated fruits were stored with sachets of ethylene absorber containing KMnO4 or ozone at 0.1 ppm/h during 10 days at 5 °C and subsequent 4 days at 20 °C. Melons treated with 1-MCP were firmer than the rest of the samples during storage. In addition, 1-MCP reduced the yellowing of melon rind compared to other treatments. The combination of 1-MCP and EA did not offer any additional effect in comparison with 1-MCP alone. There was no significant difference between fruits stored with ethylene absorber, ozone and control samples. Ozone treatment during cold storage decreased disease severity, however, fruits exposed to ozone had more serious decay throughout storage at 20 °C, probably due to the unclean air in the chamber.

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