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Biomedical subjects

Eyal Gur

Publications and source records attributed to Eyal Gur.

30 records · Page 2Linked to original sources

The Escherichia coli DjlA and CbpA proteins can substitute for DnaJ in DnaK-mediated protein disaggregation.

The DnaJ (Hsp40) protein of Escherichia coli serves as a cochaperone of DnaK (Hsp70), whose activity is involved in protein folding, protein targeting for degradation, and rescue of proteins from aggregates. Two other E. coli proteins, CbpA and DjlA, which exhibit homology with DnaJ, are known to interact with DnaK and to stimulate its chaperone activity. Although it has been shown that in dnaJ mutants both CbpA and DjlA are essential for growth at temperatures above 37 degrees C, their in vivo role is poorly understood. Here we show that in a dnaJ mutant both CbpA and DjlA are required for efficient protein dissaggregation at 42 degrees C.

Escherichia coli↗

Transoral reconstruction of the mobile tongue, using radial forearm free flap.

Tongue resection has significant influence on the patient's quality of life, because it interferes with masticatory and speech functions and affects facial aesthetics. To avoid the disadvantages of the traditional lip-splitting used to approach partial tongue reconstruction for resection (40% of the tongue or more), we recommend a completely transoral approach, with the radial forearm free flap as a donor flap. Between 1999-2001, the suggested technique was applied in 11 patients with squamous-cell carcinoma of the mobile tongue. A follow-up of 6-30 months showed good to excellent oral function, with preservation of tongue volume, motion, and facial aesthetics. This approach seems to be preferable over the lip-split approach for the reconstruction of mobile tongue defects.

Adult↗

A novel method for liver repopulation: Heterografting of micro-liver slices in a rat model.

The field of hepatocyte transplantation is developing, with encouraging results. However, current approaches are still unsuitable for human cell therapy, and safer and more applicable methods need to be developed. We recently successfully transplanted pieces of liver tissue (slices), cut from a wild-type Fischer 344 dipeptidyl peptidase IV (DPP IV)-positive rat and introduced into the liver of a DPP IV-deficient Fischer 344 rat. One month after the procedure, positive DPP IV enzymatic activity was detected in transplanted liver slices. These results suggest that transplantation of tissue slices is feasible and safe and could serve as a promising alternative to hepatocyte transplantation.

Animals↗

[The subcranial approach for tumors involving the anterior skull base].

The technical approach for anterior skull base tumors has progressed considerably during the last decade. In the classical combined craniofacial resection (CFR) technique, anterior skull base lesions have been approached through bi-frontal craniotomy coupled with Weber-Ferguson and related modifications incisions. The purpose of this work is to present our experience with the subcranial approach for treatment of anterior skull base tumors. During the years 1994-2002, 64 patients underwent 72 procedures of anterior skull base tumor resection via the subcranial approach. The ages of the patients ranged from 2 to 81 years (mean 42 years). Twenty-nine cases involved malignant tumors (40%), and 43 cases involved benign tumors (60%). The most common benign pathology was meningioma (n = 12) and the most common malignant tumor was squamous cell carcinoma (n = 8). The principle skull base reconstruction procedure was performed using a multi-layered fascia: limited defects of the dura were reconstructed with the use of temporalis fascia, whereas reconstruction of large dural defects was performed using a multi-layered fascia lata sheath. Reconstruction of significant bony defects was achieved by utilizing a split calvarial bone graft, posterior sinus wall, or titanium mash covered with pericranial flap. Postoperative follow-up (26 months in average) revealed that 76% of the patients are without evidence of disease, 14% are alive with disease, 3% died of their diseases and 7% died of unrelated causes. Twenty-seven patients (44%) have suffered from anosmia following the operation. The rate of severe complications was 5.6%, and included meningitis (n = 2), cerebrospinal fluid rhinorrhea (n = 1) and tension pneumocephalus (n = 1). We conclude that the extirpation of anterior skull base tumors via the subcranial approach is simple, reproducible and reliable, and is associated with reasonable complication rates.

Adolescent↗

Lymphoscintigraphy for sentinel node mapping using a hybrid SPECT/CT system.

UNLABELLED: Lymphoscintigraphy is performed before sentinel node (SN) biopsy for SN mapping. It is of clinical importance mainly if the tumor is located in body parts with ambiguous lymph node drainage. The purpose of this study was to assess the clinical benefit of fused SPECT/CT images to planar images for SN mapping. METHODS: Thirty-four consecutive patients with cutaneous malignant melanoma (n = 28) and squamous cell carcinoma (n = 6) and scheduled for SN biopsy were enrolled. Primary tumors were located in the trunk (n = 12), in the extremities (n = 12), in the head and neck (n = 9), and in the penis (n = 1). Scintigraphy was performed using a hybrid gamma-camera/low-dose CT system. Planar images and fused SPECT/CT images were interpreted separately. RESULTS: SPECT/CT identified multiple draining basins in 6 of 12 patients (50%) with trunk melanoma and in 3 of 9 patients (33%) with head and neck melanoma or mucosal tumor. In 9 of 21 patients (43%) with a primary tumor located in the head and neck or trunk region, SPECT/CT-fused images identified SNs that were missed on planar images, 2 of which were involved with tumor. Three of the 9 nodes were located close to the injection site and were hidden by its scattered radiation, and 2 were in-transit nodes. Another 4 nodes, identified on fused images only, were located in an additional basin to those identified on planar images. Fused images were of no added value either in patients with limb melanoma or in a patient with a penile melanoma. CONCLUSION: SPECT/CT SN mapping provides additional data that are of clinical relevance to SN biopsy in patients with trunk or head and neck melanoma and in patients with mucosal head and neck tumor.

Adult↗

Skull base reconstruction after anterior subcranial tumor resection.

OBJECT: The goal of this study was to demonstrate the efficacy of a simple and reliable technique for anterior skull base and craniofacial reconstruction in patients who have undergone excision of tumors via the subcranial approach. METHODS: There were 63 patients who had undergone 71 anterior skull base resections of tumors via the aforementioned approach. Twenty-nine cases (41%) involved malignant tumors and 42 (59%) involved benign tumors. Reconstruction of the anterior skull base was performed by a single team who used double-layer fascial graft. Limited dural defects were reconstructed using the temporalis fascia, whereas large anterior skull base defects were reconstructed using a fascia lata sheath. Reconstruction was achieved without the support of bone graft or titanium mesh and without pericranial, galeal, or free flaps. Pericranial flap wrapping of the frontonasoorbital segment was performed to prevent osteoradionecrosis if postoperative radiotherapy was planned. The incidence of cerebrospinal fluid (CSF) leakage, intracranial infection, and tension pneumocephalus was 5.6%. Histopathological examination of fascia lata grafts obtained in patients who had undergone a second procedure demonstrated integration of vascularized fibrous tissue to the graft, as well as local proliferation of a newly formed vascular layer embedding the fascial sheath. CONCLUSIONS: The use of a double-layer fascial graft alone was adequate for prevention of CSF leakage, meningitis, tension pneumocephalus, and brain herniation. The double-layer fascial flap provided a simple and reliable means for anterior skull base reconstruction after en bloc resection of both malignant and benign tumors.

Adolescent↗

Protein aggregation in Escherichia coli: role of proteases.

Protein aggregation is involved in several human diseases, and presumed to be an important process in protein quality control. In bacteria, aggregation of proteins occurs during stress conditions, such as heat shock. We studied the protein aggregates of Escherichia coli during heat shock. Our results demonstrate that the concentration and diversity of proteins in the aggregates depend on the availability of proteases. Aggregates obtained from mutants in the Lon (La) protease contain three times more protein than wild-type aggregates and show the broadest protein diversity. The results support the assumption that protein aggregates are formed from partially unfolded proteins that were not refolded by chaperones or degraded by proteases.

ATP-Dependent Proteases↗

In vivo aggregation of a single enzyme limits growth of Escherichia coli at elevated temperatures.

The formation of protein aggregates is associated with unfolding and denaturation of proteins. Recent studies have indicated that, in Escherichia coli, cellular proteins tend to aggregate when the bacteria are exposed to thermal stress. Here, we show that the aggregation of one single E. coli cytoplasmic protein limits growth at elevated temperatures in minimal media. Homoserine trans-succinylase (HTS), the first enzyme in the methionine biosynthetic pathway, aggregates at temperatures higher than 44 degrees C in vitro. Above this temperature, we can also observe in vivo aggregation that results in the complete disappearance of the enzyme from the soluble fraction. Moreover, reducing the in vivo level of HTS aggregation enables growth at non-permissive temperatures. This is the first demonstration of the physiological role of aggregation of a specific protein in the growth of wild-type bacteria.

Acyltransferases↗

Chronic radiodermatitis injury after cardiac catheterization.

The authors present two patients in whom chronic radiodermatitis developed after repeated cardiac catheterization and coronary angioplasty procedures, with no indication of malignancy. In one patient, after other therapeutic methods were unsuccessful in alleviating his symptoms, the authors excised the lesion with wide surgical margins and skin grafted the area. The mere purpose was to free the patient from the unrelenting pain and discomfort. In this case, the authors achieved complete success in wound healing but only partial success in pain relief.

Aged↗

Immature leukemic CD34+CXCR4+ cells from CML patients have lower integrin-dependent migration and adhesion in response to the chemokine SDF-1.

Chronic myelogenous leukemia (CML), a malignant myeloproliferative disorder originating from a pluripotent stem cell expressing the bcr-abl oncogene, is characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow (BM) into the circulation. Moreover, immature CD34+ CML cells have lower adhesion to stromal cells and fibronectin as well as lower engraftment potential in severe combined immunedeficient (SCID) and nonobese diabetic (NOD)/SCID mice than normal CD34+ cells. We report in this study that leukemic Philadelphia chromosome-positive (Ph+)CD34+ cells from newly diagnosed CML patients that express the chemokine receptor CXCR4 migrate in response to stromal-derived factor-1 (SDF-1). However, normal Ph-CD34+CXCR4+ cells derived from the same patient have significantly higher migration levels toward SDF-1. In contrast to their transwell migration potential, the SDF-1-mediated integrin-dependent polarization and migration of the Ph+CD34+CXCR4+ cells through extracellular matrix-like gels were significantly lower than for normal cells. Concomitantly, binding of these cells to vascular cell adhesion molecule-1 or fibronectin, in the presence of SDF-1, was also substantially lower. These findings suggest a major role for SDF-1-mediated, integrin-dependent BM retention of Ph+CD34+ cells.

Antigens, CD34↗