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J I Cohen

Publications and source records attributed to J I Cohen.

At least 19 recordsLinked to original sources
PubMed2001

Activation of NK cell-mediated cytotoxicity by a SAP-independent receptor of the CD2 family.

Some CD2 family receptors stimulate NK cell-mediated cytotoxicity through a signaling pathway, which is dependent on the recruitment of an adapter protein called SLAM-associated protein (SAP). In this work we identify a novel leukocyte cell surface receptor of the CD2 family called CD2-like receptor activating cytotoxic cells (CRACC). CRACC is expressed on cytotoxic lymphocytes, activated B cells, and mature dendritic cells, and activates NK cell-mediated cytotoxicity. Remarkably, although CRACC displays cytoplasmic motifs similar to those recruiting SAP, CRACC-mediated cytotoxicity occurs in the absence of SAP and requires activation of extracellular signal-regulated kinases-1/2. Thus, CRACC is a unique CD2-like receptor which mediates NK cell activation through a SAP-independent extracellular signal-regulated kinase-mediated pathway.

Amino Acid Sequence↗
PubMed2001

Infection with Langat Flavivirus or expression of the envelope protein induces apoptotic cell death.

Langat (LGT) flavivirus, derived from infectious full-length cDNA clone 636, was investigated for its apoptotic activities in mouse neuroblastoma (Neuro-2a) and simian kidney (Vero and LLC-MK(2)) cells. The hallmark of apoptosis, cleavage of cellular DNA, was observed 48 h after infection of Vero, LLC-MK(2), and Neuro-2a cells by electrophoresis analysis. Apoptosis in infected cells was also confirmed by TUNEL assay. LGT-infected Neuro-2a cells showed an increase in caspase-3-like protease (DEVDase) activity. Expression of the major envelope glycoprotein (E) alone reduced cell viability in both Vero and Neuro-2a cells, and the baculovirus P35 protein, which inhibits multiple caspases, completely blocked this effect. Cleavage of cellular DNA was observed in E gene-transfected Vero cells by TUNEL assay. Expression of E protein or caspase-9 resulted in activation of caspase-3-like proteases in Neuro-2a cells. The caspase-3-like protease specific inhibitor, Ac-DEVD-CHO peptide, partially inhibited E protein- or caspase-9-induced apoptosis in Neuro-2a cells. These observations indicate that infection of cells with LGT virus or expression of LGT virus E protein induces apoptosis through a caspase-3-like protease pathway.

Animals↗
PubMed2001

Varicella-zoster virus (VZV) ORF65 virion protein is dispensable for replication in cell culture and is phosphorylated by casein kinase II, but not by the VZV protein kinases.

The unique short region of varicella zoster virus (VZV) encodes four genes. One of these, ORF65, is predicted to encode an 11-kDa protein. Antibody to ORF65 protein immunoprecipitated a 16-kDa protein from the membrane fraction of VZV-infected cells. ORF65 protein was shown to be phosphorylated by casein kinase II. The VZV ORF47 or ORF66 protein kinases were not required for phosphorylation of ORF65. VZV with a large deletion in ORF65 was constructed and was shown to be dispensable for replication of virus in cell culture. The herpes simplex virus homolog of VZV ORF65 has been reported to be located in the nucleus of infected cells and in virions as a tegument protein, whereas the pseudorabies virus homolog is located in the Golgi apparatus of infected cells and in virions as a type II membrane protein. The ORF65 protein localized to the Golgi apparatus in virus-infected cells and was located in virions, most likely as a type II membrane protein. Thus, VZV ORF65 more closely resembles its pseudorabies virus homolog in its localization in infected cells and virions.

Animals↗
PubMed2001

Distinct interactions of the X-linked lymphoproliferative syndrome gene product SAP with cytoplasmic domains of members of the CD2 receptor family.

X-linked lymphoproliferative syndrome (XLP; Duncan's disease) is a primary immunodeficiency disease that manifests as an inability to regulate the immune response to Epstein-Barr virus (EBV) infection. Here we examine the ability of the product of the gene defective in XLP, SAP (DSHP/SH2D1A), to associate with the cytoplasmic domains of several members of the CD2 subfamily of cell surface receptors, including SLAM, 2B4, and CD84. While recruitment of SAP to SLAM occurred in a phosphorylation-independent manner, SAP was found to bind preferentially to tyrosine-phosphorylated cytoplasmic domains within 2B4 and CD84. Missense or nonsense mutations in the SAP open reading frame were identified in five of seven clinically diagnosed XLP patients from different kindreds. Four of these variants retained the ability to bind to the cytoplasmic tails of SLAM and CD84. While ectopic expression of wild-type SAP was observed to block the binding of SHP-2 to SLAM, mutant SAP derivatives that retained the ability to bind SLAM did not inhibit recruitment of SHP-2 to SLAM. In contrast, SAP binding to CD84 had no effect on the ability of CD84 to recruit SHP-2, but instead displaced SHP-1 from the cytoplasmic tail of CD84. These results suggest that mutations in the gene encoding the XLP protein SAP lead to functional defects in the protein that include receptor binding and SHP-1 and SHP-2 displacement and that SAP utilizes different mechanisms to regulate signaling through the CD2 family of receptors.

Antigens, CD↗
PubMed2001

Mutagenesis of the varicella-zoster virus genome: lessons learned.

The varicella-zoster virus (VZV) genome encodes at least 70 genes. We have developed a cosmid based system to inactivate individual viral genes or to insert foreign genes into the genome. We have shown that many VZV genes are not required for replication of the virus in cell culture. Several of these genes, including VZV ORF61, ORF47, and ORF10, have unexpected phenotypes in cell culture and differ from their homologs in the better studied herpes simplex virus (HSV). We have also used the Oka strain of VZV as a live virus vaccine vector. Guinea pigs vaccinated with recombinant VZV expressing HSV-2 glycoprotein D and challenged with HSV-2 have reduced severity of primary genital herpes and reduced mortality compared to animals receiving parental VZV. Recently we have inserted the human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) glycoprotein 160 genes into the Oka strain of VZV and have shown that these proteins are expressed in recombinant virus-infected cells. Thus, directed mutagenesis of the VZV genome is providing new insights into viral pathogenesis and may provide new candidate vaccines.

Animals↗
PubMed2001

Use of the radial forearm free tissue flap to treat persistent stricture after esophagogastrectomy.

BACKGROUND: Persistent stricturing or anastomotic leakage at the cervical esophagogastric anastomosis can be a troublesome complication of gastric pull-up procedures. When the stricture is the result of ischemia of the stomach, the strictures are long and often not responsive to dilatation and require large operations such as jejunal interposition or replacement with colonic pull-up. In this report we describe the use of a radial forearm flap to patch strictures. METHODS: The radial forearm flap is a fascia cutaneous flap taken from the forearm and based on the radial artery and its venae comitantes. The advantages of this flap are that it is thin and pliable, conforms easily, has excellent reliability due to the size of the feeding vessels, and has a relatively long pedicle. The vascular anastomosis can be made to several arteries and veins within the neck. The epithelial component can be made in sizes up to 10 by 20 cm. RESULTS: We have used the radial forearm flap to patch strictures in 6 patients with persistent complex strictures in the cervical region after esophagectomy. Results were excellent in 4 patients (able to eat liquids and solids without problems) and good in 1 patient (liquids okay, some problem with solids), and 1 patient died postoperatively. Follow-up is 4 months to 7 years. CONCLUSIONS: The radial forearm flap is an excellent option for handling persistent stricture after esophagogastrectomy. In many instances, this flap can be used in lieu of a jejunal interposition flap and obviates a laparotomy to harvest jejunum. The flap fits easily into the neck and conforms to the space.

Adult↗
PubMed2001

A prospective comparison of scalpel versus bipolar scissors in the elevation of radial forearm fasciocutaneous free flaps.

OBJECTIVES/HYPOTHESIS: The radial forearm fasciocutaneous free flap has become the workhorse for reconstruction of head and neck ablative defects. A location distal to the head and neck allows this flap to be elevated concurrent with the ablation. Most commonly, the flap is elevated under tourniquet control. This involves a primary ischemic insult with a certain amount of hemorrhage after the tourniquet is released. Bipolar scissors are a new method of dissection. They may allow for a speedier dissection with a concomitant decrease in ischemic time. Their hemostatic properties may control hemorrhage after use of the tourniquet. STUDY DESIGN: A prospective study of patients undergoing radial forearm free flaps over a 12-month period at a tertiary care referral center was undertaken. RESULTS: Forty patients were entered into the study, flaps were elevated with scalpel (20) and with bipolar scissors (20). Mean time under tourniquet was 39 minutes (range, 30-56 min) with scalpel compared with 27 minutes (range, 21-31 min) with bipolar scissors (P <.001). Total mean time of elevation (including control of hemostasis and pedicle dissection) for scalpel elevation was 50 minutes (range, 35-61 min) compared with 32 minutes (range, 20-41 min) for bipolar scissors elevation (P <.001). Mean blood loss was 46 mL (range, 15-110 mL) in the scalpel elevation group compared with 14 mL (range, 0-50 mL) in the bipolar scissors elevation group (P <.001). Complications at the donor site were equal between groups. CONCLUSIONS: Bipolar scissors are a safe, efficient method for elevating radial forearm free flaps.

Dissection↗
PubMed2001

Effect of anemia on the fasciocutaneous flap survival in a rat model.

OBJECTIVE/HYPOTHESIS: Ablative surgery for head and neck cancer that creates large composite defects often results in a significant decrease in the hematocrit level. These defects are best reconstructed with a microvascular free tissue transfer. Effect of the decreased hematocrit on microvascular flap survival is controversial. The purpose of this study was to assess the effect of isovolemic anemia on flap survival in a rat model. STUDY DESIGN: Prospective analysis. METHODS: Ninety rats were used (30 control and 60 experimental animals). Experimental animals were rendered anemic by blood draw and volume resuscitated with either a colloid (30 animals) or crystalloid (30 animals) solution. In all animals a ventral fasciocutaneous flap was raised. A vascular clamp was applied to the arteriovenous pedicle, and different ischemic times were allowed to elapse before clamp removal. Flap survival was assessed at 5 days. Probit analysis was performed for the three animal groups. RESULTS: A significantly increased probability of the flap survival was found in the anemic animals compared with the control group (P < or = .05). No difference was found between the colloid and crystalloid resuscitation groups. CONCLUSIONS: A decreased hematocrit level increases fasciocutaneous flap tolerance to ischemia and significantly increases the primary ischemic time in the ventral flap clamp model in rats. Fluid replacement with either crystalloid or colloid produces identical results.

Anemia↗
PubMed2001

MRI detection of cervical metastasis from differentiated thyroid carcinoma.

BACKGROUND: With the advent of the use of serum thyroglobulin as a marker for the recurrence of well-differentiated thyroid cancer (WDTC) after total thyroidectomy, clinicians are increasingly faced with the diagnostic dilemma of detecting the site of recurrence in thyroglobulin-positive patients with normal clinical examinations. The high protein content of this thyroglobulin may make it specifically detectable by magnetic resonance (MR) imaging. OBJECTIVE: To determine the ability of MR imaging to detect the presence of metastatic WDTC in cervical lymph nodes. STUDY DESIGN: Retrospective cohort. METHODS: Blinded review by two independent head and neck radiologists of 34 head and neck MR scans obtained from 26 patients with thyroid cancer (12 with primary disease and 14 with recurrent disease) all of whom subsequently underwent surgical removal of the lymph nodes considered at risk by imaging. RESULTS: The average overall percent sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MR imaging were 95%, 51%, 84%, 78%, and 83%, respectively. The concordance between the two radiologists was 69%. There was no overall difference in the ability of the MR scan to detect the presence of disease in the upper jugular, lower jugular, or paratracheal nodal stations. However, it was more useful for papillary carcinoma (PPV 86%, accuracy 85%) than for follicular carcinoma or the follicular variant of papillary carcinoma (PPV 63%, accuracy 67%). CONCLUSION: MR imaging is a sensitive and accurate technique for the detection of WDTC, particularly papillary carcinoma, metastatic to cervical lymph nodes. However, the lower specificity of this modality precludes its use as a screening tool.

Adenocarcinoma, Follicular↗
PubMed2001

Tracheoesophageal puncture in the office setting with local anesthesia.

Tracheoesophageal puncture (TEP) with voice prosthesis placement is currently the method of choice for vocal rehabilitation of patients who have undergone total laryngectomy. Occasionally, secondary TEP needs to be performed. We have used a TEP technique that is performed in the clinic setting with local anesthesia and no sedation. The purpose of this study was to review our technique and experience and to evaluate results, complications, and patients' acceptance of the procedure. We performed a retrospective chart review of the records of 14 patients who had undergone total laryngectomy and secondary TEP placement in the clinic setting. The procedure was well tolerated. The voice results were fair to good in 11 of 12 patients. There was 1 complication, a false passage between the trachea and the esophagus. Voicing was immediate in 12 of the 14 cases. We conclude that TEP can be performed in the office setting with local anesthesia. The voice results are excellent, and the procedure is well tolerated by the patient. Proper patient selection and regular follow-up by a speech-language pathologist are important.

Adult↗
PubMed2000

Accuracy of computed tomography in determining the presence or absence of metastatic retropharyngeal adenopathy.

OBJECTIVE: To decide the accuracy of computed tomography in determining the presence or absence of metastatic retropharygeal adenopathy in patients with squamous cell carcinoma of the head and neck. DESIGN: A comparison of the results of retrospective blinded review of preoperative computed tomographic scans with the histologic findings of retropharyngeal node dissection at the time of surgery. SETTING: Academic tertiary care center. PATIENTS: Twenty-six patients with advanced stage squamous cell carcinoma of the head and neck. MAIN OUTCOME MEASURES: Computed tomographic findings and histologic results of retropharyngeal node dissection. RESULTS: The retropharyngeal nodes were pathologically positive for metastasis in 6 (23%) of the 26 patients. The radiologist (J.M.T.) correctly read the scan in 3 of 6 patients with histologically proved metastasis, and in 14 of 20 patients with histologic features negative for metastasis. The sensitivity of the radiologist reading was 50%, and the specificity was 70%. The positive predictive value was 33%, and the negative predictive value was 82%. CONCLUSION: The presence of retropharyngeal node metastasis cannot be determined by computed tomographic imaging alone. Arch Otolaryngol Head Neck Surg. 2000;126:1478-1481

Adult↗
PubMed2000

Sensory changes associated with selective neck dissection.

OBJECTIVE: To evaluate sensory changes in the head and neck region associated with selective neck dissection with or without preservation of cervical root branches. DESIGN: Retrospective cohort study. SETTING: University tertiary referral hospital and a Veterans Affairs hospital. PATIENTS: Fifty-seven patients who had undergone 84 neck dissections with or without preservation of the sensory cervical root branches 3 or more months before evaluation. INTERVENTIONS: Questionnaire combined with head and neck sensory examination. MAIN OUTCOME MEASURES: Neck and facial sensory function. RESULTS: Neck dissections with preservation of the cervical rootlets were most likely to be associated with a small area of anesthesia in the upper neck below the body of the mandible and anterior to the mid-body of the mandible (P=.03). Neck dissections without rootlet-preserving technique increased the area of anesthesia to include all other areas of the neck (P= .02). CONCLUSIONS: Preservation of the cervical root branches resulted in a small, limited, and uniform area of the neck rendered permanently anesthetic. Conversely, sacrifice of the nerve branches led to a pattern of anesthesia involving the entire neck.

Aged↗
PubMed2000

Genetic polymorphisms in head and neck cancer risk.

OBJECTIVE: To assess whether genetic polymorphisms implicated as risk factors for other tobacco-associated malignancies are associated with altered risk of head and neck squamous cell carcinoma. DESIGN: Case-control study. SUBJECTS: One hundred sixty patients with head and neck squamous cell carcinoma recruited from a university-based head and neck oncology clinic and 149 population-based controls. METHODS: Genotyping of the CYP1A1 (Ile462Val), GSTM1 (null), GSTP1 (Ile105Val), GSTT1 (null), and P53 (Arg72Pro) genes was performed by polymerase chain reaction-based techniques on DNA prepared from peripheral blood. In addition, a questionnaire was used to collect demographic information from each subject. RESULTS: Cases were significantly older (p <.0001) and had significantly greater tobacco use (p <.0001) and were more likely to be male (p <.0001) than were control subjects, thus confirming known risk factors for this disease. When cases and controls were compared by simple chi-square analysis, only the frequency of CYP1A1 (Ile462Val) polymorphism was significantly different between cases and controls (OR =.42; 95% CI =.18-.99; p <.04). However, with a logistic regression model to control for known risk factors, we were unable to demonstrate a significant association with head and neck cancer for any of the polymorphisms tested, including CYP1A1. CONCLUSIONS: This population fails to identify a relationship between the above-mentioned polymorphisms and head and neck cancer.

Carcinoma, Squamous Cell↗
PubMed2000

The relative value of fine-needle aspiration and imaging in the preoperative evaluation of parotid masses.

BACKGROUND: To establish the sensitivity, specificity, and accuracy of imaging and fine-needle aspiration (FNA), alone or in combination, in distinguishing benign from malignant histologic findings for parotid lesions. METHODS: Retrospective blinded review of preoperative imaging and FNA studies of parotid masses and comparison with histologic findings after excision. RESULTS: Forty-eight patients were identified (13 with CT, 35 with MRI); 23 (48%) of the lesions were malignant, 25 (52%) were benign. MRI, CT, and FNA misclassified 17%, 46%, and 21% of the lesions, respectively. The sensitivity/specificity/accuracy of these tests for detecting malignant lesions were as follows: MRI (88%,77%,83%), CT (100%,42%, 69%), and FNA (83%,86%,85%) and were not significantly different. Combinations of imaging and FNA were not significantly better in detecting malignancy. CONCLUSIONS: Imaging and FNA are comparable in their ability to correctly identify malignant parotid lesions preoperatively. Combining these two modalities yields no advantage in terms of specificity, sensitivity, or accuracy of a malignant diagnosis.

Biopsy, Needle↗
PubMed2000

Patients with X-linked lymphoproliferative disease have a defect in 2B4 receptor-mediated NK cell cytotoxicity.

Patients with the X-linked lymphoproliferative disorder (XLPD) are unable to control Epstein-Barr virus (EBV)-induced infections and lymphoproliferation. This disease is caused by a deficit of SAP, an adapter protein involved in the signal transduction of several cell surface receptors of the CD2 superfamily. One of these receptors, called 2B4, is expressed on NK cells, cytotoxic T cells and myeloid cells and activates NK cell cytotoxicity. Here we show that XLPD patients have a defect of 2B4 receptor-mediated NK cell cytotoxicity. This defect may contribute to the pathogenesis of XLPD by reducing NK cell lysis of EBV-infected B cells.

Antigens, CD↗
PubMed2000

A new approach to vaccination: polymorphic vaccines for RNA viruses.

Conventional vaccines consist of a very large number of virtually identical molecules. While these have been extremely effective for prevention against viral diseases, development of vaccines against rapidly changing pathogens such as human immunodeficiency virus (HIV) and hepatitis C virus has proved to be more difficult. We propose a new approach to vaccination against these rapidly mutating pathogens by the use of vaccines consisting of a set of highly polymorphic recombinant molecules.

AIDS Vaccines↗