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result(s) for
"Unal, Ekrem"
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Microfluidic Chip based direct triple antibody immunoassay for monitoring patient comparative response to leukemia treatment
2020
We report a time and cost-efficient microfluidic chip for screening the leukemia cells having three specific antigens. In this method, the target blast cells are double sorted with immunomagnetic beads and captured by the 3rd antibody immobilized on the gold surface in a microfluidic chip. The captured blast cells in the chip were imaged using a bright-field optical microscope and images were analyzed to quantify the cells. First sorting was performed with nano size immunomagnetic beads and followed by 2nd sorting where micron size immunomagnetic beads were used. The low-cost microfluidic platform is made of PMMA and glass including micro size gold pads. The developed microfluidic platform was optimized with cultured B type lymphoblast cells and tested with the samples of leukemia patients. The 8 bone marrow samples of 4 leukemia patients on the initial diagnosis and on the 15th day after the start of the chemotherapy treatment were tested both with the developed microfluidic platform and the flow cytometry. A 99% statistical agreement between the two methods shows that the microfluidic chip is able to monitor the decrease in the number of blast cells due to the chemotherapy. The experiments with the patient samples demonstrate that the developed system can perform relative measurements and have a potential to monitor the patient response to the applied therapy and to enable personalized dose adjustment.
Journal Article
Human FCHO1 deficiency reveals role for clathrin-mediated endocytosis in development and function of T cells
by
Sykora, Karl-Walter
,
Liu, Yanshan
,
Keppler, Oliver T.
in
631/208/2489/144
,
631/250/1619/554
,
631/80/313/1461
2020
Clathrin-mediated endocytosis (CME) is critical for internalisation of molecules across cell membranes. The FCH domain only 1 (FCHO1) protein is key molecule involved in the early stages of CME formation. The consequences of mutations in
FCHO1
in humans were unknown. We identify ten unrelated patients with variable T and B cell lymphopenia, who are homozygous for six distinct mutations in
FCHO1
. We demonstrate that these mutations either lead to mislocalisation of the protein or prevent its interaction with binding partners. Live-cell imaging of cells expressing mutant variants of FCHO1 provide evidence of impaired formation of clathrin coated pits (CCP). Patient T cells are unresponsive to T cell receptor (TCR) triggering. Internalisation of the TCR receptor is severely perturbed in FCHO1-deficient Jurkat T cells but can be rescued by expression of wild-type FCHO1. Thus, we discovered a previously unrecognised critical role of FCHO1 and CME during T-cell development and function in humans.
FCH domain only 1 (FCHO1) is a key molecule involved in clathrin-mediated endocytosis (CME). Here, the authors report homozygous FCHO1 mutations in individuals with variable T and B cell lymphopenia, which are associated with loss-of-function of FCHO1 and impaired formation of clathrin-coated pits in T cells.
Journal Article
Thauvin-Robinet-Faivre Syndrome: A FIBP Variant in an Adolescent with Segmental Overgrowth and Thyroid Carcinoma
2026
Overgrowth syndromes are rare genetic disorders arising from alterations in the growth factors pathway. These syndromes can present as generalized overgrowth, characterized by macrosomia and excessive height compared to peers, or partial overgrowth syndromes, where specific body regions exhibit disproportionate growth often accompanied by vascular anomalies. Both forms are associated with an increased risk of tumor development. The
gene plays a critical role in cell proliferation and differentiation by interacting with growth factors. In this article, we present a case of Thauvin-Robinet-Faivre syndrome (TROFAS) in a 16-year-old girl, diagnosed with homozygous NM_004214.5 c.412-3_415dup (p. Asp139AIafsTer3) variant in the
gene. This case exhibits phenotypic features and tumor development, including thyroid follicular carcinoma and parotid mucoepidermoid carcinoma, that have not been previously reported in association with this syndrome. Recent studies have implicated
gene defects in overgrowth syndromes, with only a limited number of cases described globally. This case expands the known clinical and tumor spectrum associated with TROFAS, providing new insights into the pathophysiology of this rare disorder.
Journal Article
Curing the “Incurable”: First Successful Hematopoietic Stem Cell Transplantation in Severe Hereditary Spherocytosis with Homozygous SPTA1 Variant and Hepatic Fibrosis
by
Ünal, Ekrem
,
Karakükcü, Musa
,
Özcan, Alper
in
hemolytic anemia
,
hereditary spherocytosis
,
Letter to the Editor
2026
Journal Article
A pilot study for treatment of severe COVID-19 pneumonia by aerosolized formulation of convalescent human immune plasma exosomes (ChipEXO™)
by
Gökdemir, Nur Seda
,
Bozkurt, Batuhan Turhan
,
Uygut, Muhammet Ali
in
Acute toxicity
,
Allergies
,
Bacterial infections
2022
This is a single-center prospective, open-label, single arm interventional study to test the safety and efficacy of recently described ChipEXO™ for severe COVID-19 pneumonia. The ChipEXO™ is a natural product derived from convalescent human immune plasma of patients recovered from moderate COVID-19 infection. In September 2021, 13 patients with pending respiratory failure were treated with ChipEXO™ adapted for aerosolized formulation delivered via jet nebulizer. Patients received 1-5x10 10 nano vesicle/5 mL in distilled water twice daily for five days as an add-on to ongoing conventional COVID-19 treatment. The primary endpoint was patient safety and survival over a 28-day follow-up. The secondary endpoint was longitudinal assessment of clinical parameters following ChipEXO™ to evaluate treatment response and gain insights into the pharmacodynamics. ChipEXO™ was tolerated well without any allergic reaction or acute toxicity. The survival rate was 84.6% and 11 out of 13 recovered without any sequel to lungs or other organs. ChipEXO™ treatment was effective immediately as shown in arterial blood gas analyses before and two hours after exosome inhalation. During the 5 days of treatment, there was a sustainable and gradual improvement on oxygenation parameters: i.e. respiratory rate (RR) [20.8% (P < 0.05)], oxygen saturation (SpO 2 ) [6,7% (P < 0.05)] and partial pressure of oxygen to the fraction of inspired oxygen (PaO 2 /FiO 2 ) [127.9% (P < 0.05)] that correlated with steep decrease in the disease activity scores and inflammatory markers, i.e. the sequential organ failure assessment (SOFA) score (75%, p < 0.05), C-reactive protein (46% p < 0.05), ferritin (58% p = 0.53), D-dimer (28% p=0.46). In conclusion, aerosolized ChipEXO™ showed promising safety and efficacy for life-threatening COVID-19 pneumonia. Further studies on larger patient populations are required to confirm our findings and understand the pathophysiology of improvement toward a new therapeutic agent for the treatment of severe COVID-19 pneumonia.
Journal Article
Diffusion weighted imaging in differentiating malignant and benign neuroblastic tumors
2016
Purpose
Our aim was to assess diffusion weighted imaging (DWI) of neuroblastic tumors and whether apparent diffusion coefficient (ADC) value may have a role in discrimination among neuroblastoma, ganglioneuroblastoma and ganglioneuroma.
Material and methods
The DWIs (
b
= 0–800 s/mm
2
) of 24 children (13 girls, 11 boys) who were diagnosed neuroblastic tumors on histopathological examination (neuroblastoma = 15, ganglioneuroblastoma = 5, ganglioneuroma = 4) were evaluated retrospectively. The ADC maps were performed by drawing freehand ROI on PACS (Sectra Workstation IDS7, Linköping, Sweden).
Results
We observed a significant decrease in ADC value of neuroblastomas 0.869 ± 0.179 × 10
−3
mm
2
/s compared to ganglioneuroblastomas 0.97 ± 0.203 × 10
−3
mm
2
/s and ganglioneuromas 1.147 ± 0.299 × 10
−3
mm
2
/s (
p
= 0.026). There was no significant difference in between ganglioneuroblastoma and ganglioneuroma (
p
= 0.16). In detecting neuroblastomas; the sensitivity, specificity, negative and positive predictive values of ADC were 74, 67, 78.6, 66 % respectively with a cut-off value of 0.93 × 10
−3
mm
2
/s.
Conclusion
Our study stands out as the most comprehensive study with larger sample size on this topic. Moreover, we are able to suggest a cut-off value which can discriminate neuroblastoma from ganglioneuroblastoma and ganglioneuroma. We believe that ADC will evolve to an objective, quantitative measurement in discrimination among malignant and benign neuroblastic tumors.
Journal Article
The diagnostic value of modified systemic ınflammation score in predicting post-operative outcomes of cutaneous melanoma patients who underwent ısolated limb perfusion
2021
Background
In-transit metastasis is considered a locoregional disease in cutaneous melanoma (CM) patients. Isolated limb perfusion (ILP) is among the treatment options in selected cases. The aim of this study was to determine the success of pre- and post-perfusion mSIS values in predicting the potential complications and the prognosis of the disease by investigating the early and long-term results of mSIS values calculated before and after ILP in CM cases with in-transit metastases.
Materials and methods
Patients who underwent ILP within the period from 2014 to 2020 in our department were retrospectively scanned. A total of 20 patients were found to undergo ILP. The scores obtained from modified inflammation score (mSIS) were formulated according to albumin (Alb) and lymphocyte to monocyte ratio (LMR) scores.
Results
The mean follow-up time was 20.47 months. Complications requiring surgical intervention developed in three patients. According to the Wieberdink local toxicity classification, the majority (70%) of the patients were found to be grade II. Based on pre-perfusion mSIS values, 8 patients were classified as mSIS 0 while six patients were classified as mSIS 1 and 2. Based on post-perfusion mSIS values, 14 patients and one patient were classified as mSIS 2 (70%) and mSIS 0, respectively. Accordingly, univariate analysis showed that mSIS 1 and mSIS 2 were negative prognostic factors for mean survival in the pre-perfusion period (HR 0.162, 95% CI 0.036–0.729;
p
= 0.018 and HR: 0.223, 95% CI 0.049–1.019;
p
= 0.053) whereas albumin (Alb) and lymphocyte to monocyte ratio (LMR) were not independent prognostic factors for mean survival.
Conclusion
The mSIS values calculated in the pre-perfusion period can give an opinion about the OS of the patients whereas post-perfusion mSIS values may predict potential surgical complications and local toxicities.
Journal Article
Do Nano-crystalline Silver-Coated Hernia Grafts Reduce Infection?
2018
Purpose
Inguinal hernia repairs are the most common interventions in adults in general surgery clinics. Depending on the type of mesh and repair, the incidence of mesh-related infection ranges from 0.6 to 8%. Methicillin-resistant
Staphylococcus aureus
is the most common microorganism causing graft infection. The aim of this study was to investigate the efficacy of nano-crystalline silver-coated polypropylene grafts against graft infection created with MRSA in rats.
Methods
A total of 60 female, Wistar albino rats were used in the study. Polypropylene grafts 1 × 1 cm in size were coated in silver ion-doped, calcium phosphate-based, antibacterial ceramic powder (NS-coated graft) to provide an antimicrobial effect. The MRSA seeding procedure was applied at the same time as surgery. In Group 1, normal graft was applied without MRSA seeding, in Group 2, normal graft with MRSA seeding, in Group 3, NS-coated graft without MRSA seeding, and in Group 4, NS-coated graft with MRSA seeding. For the groups which were to be infected, the bacteria were seeded in the surgical area during the operation. On the 7th day postoperatively, all the animals were killed. The grafts were removed and one from each group was examined under electron microscope and the others were implanted in culture medium and the number of colonies was counted after 24 h.
Results
In Groups 1 and 3, the incision site was seen to have healed on day 3, no clinical surgical area infection was seen during follow-up, and in the exploration made on the 7th day, no findings of infection were observed. In Group 2, hyperemia and collection were seen to have formed on day 3, abscess had started to form in all the rats of this group on day 4, a purulent discharge in the wound site had started in 12 animals on day 5, separation of the wound site was observed in 6 on day 6, and in the exploration on day 7, there was seen to be a fibrin and pus-rich collection around the graft in all cases. In Group 4, there were hyperemia and collection in 6 animals on day 4, and in 3 of these, abscess was seen to have formed on the 5th day. No purulent discharge or wound separation was observed. In the exploration on the 7th day, it was seen that in the animals with abscess development, the formation was of a localized abscess. The results of the cultures of the grafts removed from Groups 1 and 3 showed no production, whereas production was seen in all the grafts removed from Groups 2 and 4. Clinical surgical area infection was seen to have developed in 100% of Group 2 and in 40% of Group 4. In the comparison of the number of colonies, a statistically significantly lower number of bacteria were determined in Group 4 compared to Group 2 (
p
< 0.05). In the SEM images taken of Group 2, bacteria clusters were seen attached to the graft.
Conclusion
Consistent with previous findings in the literature, the NS-coated polypropylene graft was seen to have a significantly better bactericidal effect than the normal polypropylene graft. Development of NS-coated grafts seems to be a reliable and applicable method to reduce the incidence of postoperative graft infection.
Journal Article