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J T Parsons

Publications and source records attributed to J T Parsons.

At least 127 records · Page 7Linked to original sources
PubMed1994

CD40 signaling pathway: anti-CD40 monoclonal antibody induces rapid dephosphorylation and phosphorylation of tyrosine-phosphorylated proteins including protein tyrosine kinase Lyn, Fyn, and Syk and the appearance of a 28-kD tyrosine phosphorylated protein.

CD40 plays an important role in B cell activation, proliferation, and Ig class switching. The signal transduction pathway mediated by CD40 was studied using monoclonal antibody (mAb) 626.1 to CD40. Burkitt's lymphoma and Epstein-Barr virus-transformed B cell lines and tonsilar B lymphocytes were treated with the anti-CD40 mAb for various lengths of time. The early events triggered by CD40 were examined by monitoring the changes in tyrosine phosphorylation of cellular proteins with anti-phosphotyrosine mAb. Dephosphorylation of specific proteins ranging between 50-110 kD and the appearance of a 28-kD tyrosine phosphorylated protein were seen within 30 s in human B cell lines. The dephosphorylation was reversed and the 28-kD protein was dephosphorylated in cells stimulated for 1 min. In resting B cells, the appearance of the 28-kD phosphoprotein was observed in 30 s after the addition of the anti-CD40 mAb. The tyrosine phosphorylation of this protein persisted. The patterns of protein tyrosine phosphorylation differed from those induced by an anti-immunoglobulin M mAb. The changes in the state of tyrosine phosphorylation induced by the anti-CD40 mAb were obviated by mAb to CD45, a protein tyrosine phosphatase (PTP) or by the addition of sodium orthovanadate, a broad PTP inhibitor. They were also blocked by protein tyrosine kinase (PTK) inhibitors, herbimycin A and genistein, and PKC and protein serine/threonine kinase inhibitors, H7 and HA1004. In addition, the alteration in the tyrosine phosphorylation of PTKs Lyn, Fyn, and Syk was directly demonstrated. Engagement of CD40 for 30 s induced a transient decrease in tyrosine phosphorylation of these PTKs. These results indicate that the early events in CD40 signaling involve the complex interaction between PTP and protein kinases.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

Tyrosine phosphorylation of pp125FAK in platelets requires coordinated signaling through integrin and agonist receptors.

FAK is a focal adhesion kinase that is phosphorylated on tyrosine in activated platelets. Induction of FAK phosphorylation requires both fibrinogen binding to integrin alpha IIb beta 3 and post-occupancy events during agonist-induced platelet aggregation or platelet spreading on a fibrinogen matrix. To identify the signaling pathways necessary for tyrosine phosphorylation of FAK, we have examined the conditions that stimulate or inhibit this phosphorylation in platelets in which fibrinogen binding to alpha IIb beta 3 and platelet aggregation were induced directly with an anti-beta 3 Fab fragment (anti-LIBS6). Apyrase was added to prevent effects of the endogenous platelet agonist, ADP. Under these conditions, neither fibrinogen binding nor primary platelet aggregation was sufficient to induce FAK phosphorylation, suggesting that a second "costimulatory" event was required. Indeed, when epinephrine was added with fibrinogen and anti-LIBS6, large platelet aggregates formed and FAK phosphorylation occurred. This response was prevented by blockade of cyclooxygenase with indomethacin or thromboxane A2 receptors with SQ 30,741. A stable thromboxane A2 analogue (U46619) could substitute for epinephrine as the costimulus. Epinephrine costimulation of FAK phosphorylation was also prevented by chelation of intracellular Ca2+ with BAPTA or selective inhibition of protein kinase C (PKC) with bisindolylmaleimide, indicating that Ca2+ and PKC are necessary for FAK phosphorylation under these conditions. Epinephrine also promoted FAK phosphorylation and adhesive spreading of apyrase-treated platelets on a fibrinogen matrix. Cytochalasin D, an inhibitor of actin polymerization, blocked FAK phosphorylation under all these conditions. Thus, tyrosine phosphorylation of FAK in platelets requires coordinated signaling through occupied integrin and agonist receptors. These separate pathways may converge to increase free Ca2+ and activate PKC and thus promote the cytoskeletal reorganization required for activation of FAK.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

Focal adhesion kinase and associated proteins.

Focal adhesion kinase (pp125FAK), a protein tyrosine kinase, has recently been suggested to regulate aspects of signalling induced by integrins and by certain growth factor and hormone receptors. New studies indicate that the domains of pp125FAK regulate its interactions with integrin subunits, other protein tyrosine kinases, and the focal adhesion associated protein paxillin. Through these interactions, pp125FAK may regulate signalling via different extracellular ligands.

Animals↗
PubMed1994

Stable association of pp60src and pp59fyn with the focal adhesion-associated protein tyrosine kinase, pp125FAK.

Changes in cellular growth and dramatic alterations in cell morphology and adhesion are common features of cells transformed by oncogenic protein tyrosine kinases, such as pp60src and other members of the Src family. In this report, we present evidence for the stable association of two Src family kinases (pp60src and pp59fyn) with tyrosine-phosphorylated forms of a focal adhesion-associated protein tyrosine kinase, pp125FAK. In Src-transformed chicken embryo cells, most of the pp125FAK was stably complexed with activated pp60src (e.g., pp60(527F). The stable association of pp125FAK with pp60(527F) in vivo required the structural integrity of the Src SH2 domain. The association of pp60(527F) and pp125FAK could be reconstituted in vitro by incubation of normal cell extracts with glutathione S-transferase fusion proteins containing SH2 or SH3/SH2 domains of pp60src. Furthermore, the association of isolated SH2 or SH3/SH2 domains with in vitro 32P-labeled pp125FAK protected the major site of pp125FAK autophosphorylation from digestion with a tyrosine phosphatase, indicating that the autophosphorylation site of pp125FAK participates in binding with Src. Immunoprecipitation of Src family kinases from extracts of normal chicken embryo cells revealed stable complexes of pp59fyn and tyrosine-phosphorylated pp125FAK. These data provide evidence for a direct interaction between two cytoplasmic nonreceptor protein tyrosine kinases and suggest that Src may contribute to changes in pp125FAK regulation in transformed cells. Furthermore, pp125FAK may directly participate in the targeting of pp59fyn or possibly other Src family kinases to focal adhesions in normal cells.

Animals↗
PubMed1994

Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src.

The phosphorylation of protein tyrosine kinases (PTKs) on tyrosine residues is a critical regulatory event that modulates catalytic activity and triggers the physical association of PTKs with Src homology 2 (SH2)-containing proteins. The integrin-linked focal adhesion kinase, pp125FAK, exhibits extracellular matrix-dependent phosphorylation on tyrosine and physically associates with two nonreceptor PTKs, pp60src and pp59fyn, via their SH2 domains. Herein, we identify Tyr-397 as the major site of tyrosine phosphorylation on pp125FAK both in vivo and in vitro. Tyrosine 397 is located at the juncture of the N-terminal and catalytic domains, a novel site for PTK autophosphorylation. Mutation of Tyr-397 to a nonphosphorylatable residue dramatically impairs the phosphorylation of pp125FAK on tyrosine in vivo and in vitro. The mutation of Tyr-397 to Phe also inhibits the formation of stable complexes with pp60src in cells expressing Src and FAK397F, suggesting that autophosphorylation of pp125FAK may regulate the association of pp125FAK with Src family kinases in vivo. The identification of Tyr-397 as a major site for FAK autophosphorylation provides one of the first examples of a cellular protein containing a high-affinity binding site for a Src family kinase SH2 domain. This finding has implications for models describing the mechanisms of action of pp125FAK, the regulation of the Src family of PTKs, and signal transduction through the integrins.

Amino Acid Sequence↗
PubMed1994

Focal adhesion kinase: structure and signalling.

Studies on the attachment and spreading of cells in culture have provided valuable insights into the mechanisms by which cells transmit information from the outside to the inside of the cell. This brief review considers recent information on the role of focal adhesion-associated protein tyrosine kinases in integrin-regulated cell signalling.

Amino Acid Sequence↗
PubMed1994

External beam irradiation alone or combined with neck dissection for base of tongue carcinoma: an alternative to primary surgery.

From 1964 to 1990, 134 patients were treated at the University of Florida with continuous-course external beam irradiation, alone or followed by a planned neck dissection, for T1 (n = 17), T2 (n = 47), T3 (n = 49), or T4 (n = 21) carcinoma of the base of tongue. The 5-year rate of local control was 90% for stage T1, 92% for T2, 73% for T3, and 35% for T4. Probability of control above the clavicles at 5 years according to modified American Joint Committee on Cancer (AJCC) stage was 100% for stages I and II, 75% for stage III, 84% for stage IVa, and 52% for stage IVb. Probability of relapse-free survival at 5 years was 100% for stages I and II, 68% for stage III, 81% for stage IVa, and 37% for stage IVb. Severe complications occurred in 2% of patients. Compared with surgical resection of the primary tumor, external beam radiotherapy results in similar rates of local control and survival with a lower risk of severe complications.

Adult↗
PubMed1994

The protein tyrosine kinase substrate cortactin is differentially expressed in murine B lymphoid tumors.

Src family protein tyrosine kinases (PTKs) actively participate in signal transduction during lymphocyte activation. However, little is known about the roles of PTKs and their substrates in lymphocyte differentiation. To identify PTK substrates that may be differentially expressed during B lymphopoiesis, we screened a panel of murine B lymphoid tumor cell lines representing various developmental stages using monoclonal antibodies (MAbs) specific for pp60src substrates. A MAb specific for cortactin, a filamentous-actin binding pp60src substrate, immunoprecipitated proteins from murine plasma-cytoma cell lines but not from pre-B cell lymphoma or B cell lymphoma cell lines. We have cloned a murine cortactin cDNA which encodes a member of a family of proteins distinguished by amino-terminal repeat domains and carboxy-terminal Src Homology 3 domains. Two members of this family (cortactin and HS1) were differentially expressed in murine B lymphoid tumor cell lines; both were detected in plasmacytoma cell lines, however HS1 was additionally detected in pre-B lymphoma and B lymphoma cell lines. Cortactin RNA was detected in most murine tissues, but was not detected in B lymphocytes or plasma cells. We hypothesize that cortactin expression is associated with transformed plasma cells and not with the terminal differentiation of normal B lymphocytes to plasma cells.

3T3 Cells↗
PubMed1994

Pleomorphic adenoma: effect of tumor spill and inadequate resection on tumor recurrence.

Intraoperative tumor spill or inadequate resection may be associated with an increase in the recurrence rate of pleomorphic adenoma. An attempt was made to determine the recurrence rate when such factors were identified at the time of operation. From 1970 through 1989, 17 cases were identified in which there was a question of intraoperative tumor spill or inadequate resection of a salivary gland pleomorphic adenoma. Patients were either observed or given postoperative irradiation with a mean follow-up of 7.4 years. The overall initial local recurrence rate was 24%, and all recurrences were successfully salvaged. Inadequate resection, particularly enucleation, was predictive of local recurrence, but tumor spill was not. Postoperative irradiation after inadequate resection appeared to decrease the probability of recurrence. We conclude that recurrence of pleomorphic adenoma is not increased by tumor spill as compared with inadequate resection.

Adenoma, Pleomorphic↗
PubMed1993

Radiotherapy alone or combined with neck dissection for T1-T2 carcinoma of the pyriform sinus: an alternative to conservation surgery.

PURPOSE: We present our experience with irradiation alone or combined with neck dissection for AJCC T1-T2 pyriform sinus carcinoma and compare our results to those obtained with conservation surgery. METHODS AND MATERIALS: Seventy-three patients were treated between 1964 and 1990. All patients had a minimum of 2 years of follow-up; no patient was lost to follow-up. RESULTS: The 5-year rates of local control and ultimate local control were, for Stage T1 (17 patients), 88% and 94%; and for Stage T2 (56 patients), 79% and 91%. Patients with T2 lesions had a significantly higher rate of local control after twice-daily, compared with once-daily, irradiation (p = .04). However, a multivariate analysis of various parameters revealed that none of the variables tested significantly influenced this end point: vocal cord mobility (p = .15), once- vs. twice-daily fractionation (p = .33), T1 vs. T2 (p = .32), apex invasion (p = .58), and pretreatment CT scan (p = .67). Local control with laryngeal voice preservation was obtained in 88% of patients with T1 cancers and 80% of those with T2 cancers. Ultimate control above the clavicles at 5 years according to AJCC stage was as follows: I and II, 100%; III, 78%; IVA, 75%; and IVB, 60%. The probability of cause-specific survival at 5 years was as follows: I and II, 100%; III, 83%; and IVA and IVB, 51%. Overall, nine patients (12%) developed severe complications, one of which was fatal. CONCLUSION: Compared with available data from series using conservation surgery, radiotherapy alone or followed by neck dissection results in similar rates of local control and survival with a significantly lower risk of fatal complications.

Carcinoma↗
PubMed1993

Lhermitte's sign: incidence and treatment variables influencing risk after irradiation of the cervical spinal cord.

PURPOSE: Lhermitte's sign is a relatively infrequent sequela of irradiation of the cervical spinal cord. In this study, we sought to determine whether various treatment parameters influenced the likelihood of developing Lhermitte's sign. METHODS AND MATERIALS: Between October 1964 and December 1987, 2901 patients with malignancies of the upper respiratory tract were treated at the University of Florida. The dose of radiation to the cervical spinal cord was calculated for those patients who had a minimum 1-year follow-up. A total of 1112 patients who received a minimum of 3000 cGy to at least 2 cm of cervical spinal cord were included in this analysis. RESULTS: Forty patients (3.6%) developed Lhermitte's sign. The mean time to development of Lhermitte's sign after irradiation was 3 months, and the mean duration of symptoms was 6 months. No patient with Lhermitte's sign developed transverse myelitis. Several variables were examined in a univariate analysis, including total dose to the cervical spinal cord, length of cervical spinal cord irradiated, dose per fraction, continuous-course compared with split-course radiotherapy, and once-daily compared with twice-daily irradiation. Only two variables proved to be significant. Six (8%) of 75 patients who received > or = 5000 cGy to the cervical spinal cord developed Lhermitte's sign compared with 34 (3.3%) of 1037 patients who received < 5000 cGy (p = .04). For patients treated with once-daily fractionation, 28 (3.4%) of 821 patients who received < 200 cGy per fraction developed Lhermitte's sign compared with 6 (10%) of 58 patients who received > or = 200 cGy (p = .02). CONCLUSION: An increased risk of developing Lhermitte's sign was demonstrated for patients who received either > or = 200 cGy per fraction (one fraction per day) or > or = 5000 cGy total dose to the cervical spinal cord.

Carcinoma↗
PubMed1993

Carcinoma in situ of the glottic larynx: the role of radiotherapy.

PURPOSE: To examine the University of Florida experience with radiotherapy of carcinoma in situ of the true vocal cord and compare our results with those reported in other series using various treatment modalities. METHODS AND MATERIALS: Nineteen patients with carcinoma in situ of the true vocal cord were treated with curative intent with radiation therapy at the University of Florida between October 1964 and September 1990. All patients had a minimum 2-year follow-up. Before the radiotherapy, four patients had undergone a biopsy only, 11 patients had undergone one stripping procedure, and four patients had undergone 2 to 5 strippings. Radiation doses were between 5625 cGy and 6300 cGY (median, 5625 cGy). RESULTS: The 5-year rates of local control, ultimate local control, and local control with voice preservation were 93%, 100%, and 93%, respectively. A literature review revealed that local control rates after primary treatment with radiotherapy, laser resection, and vocal cord stripping were 84%, 68%, and 66%, respectively. CONCLUSION: Primary treatment with radiotherapy should be strongly considered for patients with carcinoma in situ of the true-vocal cord who have a recurrence after vocal cord stripping or who cannot have close follow-up after treatment.

Aged↗
PubMed1993

Elective inguinal lymph node irradiation for pelvic carcinomas. The University of Florida experience.

BACKGROUND: There is little published information pertaining to elective inguinal lymph node irradiation for carcinomas originating in the pelvis that place the inguinal lymph nodes at risk. METHODS: Between October 1964 and October 1988, 164 patients with primary carcinomas originating in the pelvis that placed the inguinal lymph nodes at risk for subclinical disease received elective inguinal lymph node irradiation at the University of Florida. All patients had a minimum follow-up of 2 years from the start of radiation therapy. Primary sites included the penis, urethra, vulva, anal canal, distal rectum (within 4 cm of the verge), and the cervix or vagina when the tumor involved the distal one-third of the vagina. In 148 patients, both groins were clinically negative; in 16 patients, one groin was positive and the other negative by clinical examination. Treatment techniques were individualized according to the primary site. Tumor doses to the inguinal lymph nodes varied, although more than 70% of patients received 4500-5000 cGy (range, 2650-6780 cGy) over 5 weeks (range, 2-7 weeks) at 180-200 cGy per fraction. Patients were excluded from the analysis of disease control in the inguinal area if they died less than 2 years from treatment with the inguinal lymph nodes continuously disease free or if they experienced recurrence at the primary site with the inguinal lymph nodes clinically negative at the time of recurrence. RESULTS: The inguinal lymph node control rate was 96% (101 of 105). No patient in whom recurrent disease developed in the inguinal lymph nodes underwent salvage therapy. CONCLUSIONS: Elective irradiation of the inguinal lymph nodes is highly effective in controlling subclinical disease from carcinomas originating in the pelvis and can be accomplished with minimal acute or long-term complications.

Adult↗
PubMed1993

Pharyngeal wall carcinoma treated with radiotherapy: impact of treatment technique and fractionation.

PURPOSE: To determine whether a modification in treatment technique and the routine use of twice-daily fractionation have influenced the likelihood of local control in carcinomas of the hypopharyngeal and/or oropharyngeal wall. METHODS AND MATERIALS: Between October 1964 and July 1990, 99 patients with invasive, previously untreated T1-T4 squamous cell carcinoma of the pharyngeal wall were treated with continuous-course, external-beam radio-therapy with curative intent at the University of Florida. All patients had a minimum 2-year follow-up. RESULTS: The 2-year local control rates for patients treated with once-daily vs. twice-daily fractionation were T1, 100% each; T2, 67% vs. 92%; T3, 43% vs. 80%; and T4, 17% vs. 50%. The 2-year local control rates for patients treated with our former technique (posterior border placed at middle of the vertebral body when the portals were reduced off the spinal cord) vs. our current, modified technique (posterior border placed at posterior edge of the vertebral body) were T1, 100% each; T2, 57% vs. 100%; T3, 46% vs. 73%; and T4, 29% vs. 75%. The parameters of T stage, fractionation schedule, primary site, (oropharynx vs. hypopharynx) treatment technique, and lateral vs. posterior pharyngeal wall location were evaluated in a multivariate analysis for the end point of local control. T stage (p = .003), fractionation schedule (p = .001), and primary site (p = .028) were of independent prognostic significance. CONCLUSION: Twice-daily fractionation was the most important treatment-related variable in this patient population.

Aged↗