Biomedical subjects

Vishal Mehta

Publications and source records attributed to Vishal Mehta.

6 recordsLinked to original sources

PubMed2006

Human intestinal intraepithelial lymphocytes keep TNF alpha levels low by cell uptake and feedback inhibition of transcription.

BACKGROUND: Human intestinal intraepithelial lymphocytes (IELs) are mainly TCRalphabeta(+)CD8(+) T cells, juxtaposed between epithelial cells. Their release of TNFalpha, a cytokine that is toxic to the epithelium, is likely to be tightly regulated. This study documents a novel mechanism to keep TNFalpha levels low with stimuli that cause large fluctuations in IFNgamma release. METHODS: IELs were stimulated with combinations of IL-2, IL-12, and IL-15, without TCR ligation. TNFalpha and IFNgamma production was assessed at both the mRNA and protein levels. Uptake of both cytokines was analyzed by radioligand binding. RESULTS: By 72h with IL-15, IFNgamma concentrations increased markedly, while TNFalpha remained low. With IL-12 supplementation, IFNgamma increased 10-fold, while TNFalpha remained low. Initially, IELs had similar amounts of transcripts for IFNgamma and TNFalpha, indicating equivalent synthetic rates. Two events explain the low extracellular accumulation of TNFalpha. First, IELs took up 25-30% of bound (125)I-TNFalpha without undergoing apoptosis. In contrast, they incorporated little IFNgamma. Second, TNFalpha was under strict feedback control as shown by the reduction in transcription with the addition of TNFalpha. No feedback control was seen with IFNgamma. CONCLUSIONS: Extracellular TNFalpha, but not IFNgamma, levels are kept low by uptake of free cytokine followed by a decline in transcription, thereby avoiding accumulation of this potentially toxic cytokine.

Cells, Cultured↗

PubMed2005

Femoral artery and vein injury after cerclage wiring of the femur: a case report.

Iatrogenic injuries to the vascular system are a rare but serious complication of primary and revision hip arthroplasty. These injuries usually occur during screw or retractor placement at the acetabulum or proximal femur. Although vascular injury during the passage of cerclage wires is a fear of all surgeons, its occurrence is yet to be described. This case report describes an unusual injury to the femoral artery and vein by a cerclage wire passed around the femoral midshaft during revision total-hip arthroplasty. It underscores the need for diligent comparison of preoperative and postoperative vascular examinations and emergent vascular surgery consultation when needed to avoid disastrous complications.

Aged, 80 and over↗

PubMed2005

Flexor tendon pulley reconstruction.

Pulley reconstruction remains a challenging intellectual and technical exercise. When performed correctly, however, it can be a gratifying procedure that provides much improved function of the digit. As described in this article, there are many different techniques by which the pulley can be reconstructed. Each of these techniques has distinct advantages and disadvantages. The hand surgeon should be familiar with each of these techniques and the general principles of pulley reconstruction as laid out in this article. With this knowledge base, the treating surgeon is able to tailor the procedure performed to the exact anatomy and clinical situation of each patient. Although great strides have been made over the past half century, more clinical research is needed to determine the best technique, not just in the cadaver model, but also in the complex model of the living human hand.

Humans↗

PubMed2005

Characterization of adenovirus-mediated gene transfer in rabbit flexor tendons.

PURPOSE: Adenoviral vector-based gene therapy is a promising technique for the delivery of growth factors to tendons. The objective of this study was to determine whether rabbit flexor tendons could be transduced effectively by adenoviral vectors and whether the introduction of adenoviral vectors would cause a notable local inflammatory response. METHODS: Recombinant adenoviruses expressing green fluorescent protein (AdGFP) or BMP-13 (AdBMP-13) were constructed and 3 different viral titers (1 x 10(7), 1 x 10(8), and 1 x 10(9)) were tested in this study. The second through fifth tendons of the forepaws and hindpaws of a New Zealand white rabbit were identified surgically and injected with different viral titers of adenoviruses. The fifth tendon was used as a control. The tendons were harvested 12 days after surgery. The retrieved tendons were sectioned to measure transgene expression, as well as for histologic evaluation. RESULTS: At all tested viral titers an efficient dose-dependent transgene expression was detected in all samples at 12 days after injection. At the highest dose the injection sites were notable for lymphocytic infiltration, suggesting that injected adenoviral vectors can illicit some local inflammatory response. Lymphocytic infiltration was much less apparent, however, in the tendons injected with lower titers of adenoviral vectors. There was no evidence of a massive inflammatory response and/or cell death. CONCLUSIONS: Our findings show that adenovirus-based gene therapy is an efficient means of gene delivery to rabbit flexor tendons. Transduction efficiency of transgenes was dose dependent across the tested titers, although adenovirus-induced inflammation was notable only at the highest titer. This indicates that efficient gene transfer without notable local inflammatory response may be achieved by using the lower titers. Although adenovirus-induced inflammation can be minimized by using lower viral titers, its impact on adhesion formation in the long term remains unknown.

Adenoviridae↗

PubMed2005

Bone morphogenetic proteins for tendon injuries: an orthopedic primer.

Throughout the world, tendon injuries are a significant source of pain and disability. Most research on treating tendon injuries has been focused on developing new surgical techniques and perfecting existing ones. Recently, attention has turned to the biology of tendon healing as a means to improve the outcome of such injuries. If the biological milieu of the healing tendon can be altered to produce a stronger tendon, then clinical outcome can be improved. Use of bone morphogenetic proteins (BMPs) is one proposed method for improving the biology of tendon healing. BMPs 12, 13, and 14 have each been shown to improve tendon healing in animal models. In this article, I review BMP history, current research and future directions, and potential application in treating tendon injuries.

Animals↗

PubMedDate not supplied

The use of growth factors on tendon injuries.

Tendon injuries continue to be a vexing clinical problem faced by the upper extremity surgeon. These injuries often lead to disability and dissatisfaction for both the patient and treating physician. Advances throughout the century have focused largely on improvements in surgical techniques and therapy protocols. Recently, attention has been turned to the biologic pathways by which tendons heal and the growth factors involved in this process have been identified. There is great hope that these growth factors may one day be used to treat tendon injuries. This article provides a summary of the use of growth factors on tendon injuries including contemporary research, delivery methods, and future directions in this field.

Animals↗