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Biomedical subjects

J T Parsons

Publications and source records attributed to J T Parsons.

At least 73 records · Page 4Linked to original sources

Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site.

BACKGROUND: The purpose of this study was to evaluate the efficacy of the modern diagnostic evaluation for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site. METHODS: One hundred thirty patients were evaluated between June 1983 and June 1997. All underwent head and neck examinations, head and neck computed tomography (CT), and/or magnetic resonance imaging (MRI) scans, panendoscopies, and biopsies of head and neck mucosal sites. Twenty-four patients underwent 2-[fluorine-18]-2-deoxy-D-glucose (FDG) single photon emission computed tomography (SPECT); 34 patients underwent tonsillectomy. RESULTS: The primary site was identified in 56 patients (43%); the likelihood was increased in patients with suggestive findings on physical examination and/or radiographic evaluation. Eighty-three percent of the lesions were located in the tonsillar fossa and base of tongue. Results of FDG-SPECT scans were positive in 20 patients (83%); the primary tumor was detected in 7 patients (35%). Twelve (35%) of 34 patients who underwent tonsillectomy had a primary tumor discovered in the tonsillar fossa. Multivariate analysis of successful primary site detection revealed that suggestive findings on physical examination (p= .0225) and suggestive findings on CT and/or MRI (p = .0013) were significantly related to this end point. CONCLUSION: The primary lesion will be detected in over 40% of patients with physical examination of the head and neck and CT and/or MRI followed by panendoscopy and biopsies. Limited data pertaining to FDG-SPECT suggest that this provides additional useful information in a small subset of patients. Tonsillectomy is useful for those with suggestive findings on physical examination and/or radiographic evaluation.

Adult↗

Merkel cell carcinoma of the skin.

Merkel cell carcinoma is a rare, aggressive neuroendocrine tumor of the skin with a predisposition for local regional and distant spread. Radiotherapy after wide local excision has improved local control, but distant spread continues to be a significant problem. This is an update of our experience in the treatment of Merkel cell carcinoma at the University of Florida. Of 24 patients who were treated for Merkel cell carcinoma between 1984 and 1996, 18 patients were treated at the time of the initial diagnosis, and six were treated after local-regional recurrence. Of the 18 previously untreated patients, 13 had primary sites in the head and neck region, and five had primary sites elsewhere. Minimum follow-up was 1 year; no patient was lost to follow-up. The 5-year absolute survival, cause-specific survival, and local-regional control rates for the entire group were 27%, 31%, and 78%, respectively. Patients who were treated with radiotherapy at the time of initial presentation had 5-year absolute survival, cause-specific survival, and local-regional control rates of 38%, 44%, and 73%, respectively. Most deaths were due to distant metastasis. Site of the primary tumor (head and neck versus other) was not associated with any difference in the outcome. Of six patients who were treated at the time of local-regional recurrence, five developed distant metastasis at 3-19 months (median 8 months) from the time of treatment. One patient was alive and without evidence of disease 13 months after treatment. All patients who were treated at the time of local-regional recurrence had local-regional control after radiotherapy at 3-30 months (median 8 months). Wide local excision and radiotherapy is effective local-regional treatment for Merkel cell carcinoma of the skin, but distant metastasis remains a significant problem in this disease. The role and effectiveness of chemotherapy as part of the initial treatment remains to be defined.

Aged↗

The role of the family system in HIV risk reduction: youths with hemophilia and HIV infection and their parents. Adolescent Hemophilia Behavioral Intervention Evaluation Project (HBIEP) Study Group.

OBJECTIVE: To examine the relationship between family communication and HIV risk reduction behaviors among a multisite sample of 125 male youths (ages 12-25) with hemophilia and HIV- infection, as well as their parents. METHODS: Participants completed self-report surveys assessing communication and attitudes regarding HIV risk reduction interventions; adolescents also provided data about their sexual behaviors. RESULTS: Adolescents with parents who discuss sexual issues were more likely to report HIV status disclosure to sexual partners. Most parents were supportive of HIV risk reduction interventions for their adolescents, but the youths themselves tended to endorse only interventions that offered opportunities for recreational activities and socialization with peers. CONCLUSIONS: Findings are discussed in terms of intervention implications and the need for family systems-based programs.

Adolescent↗

Identification of a novel cortactin SH3 domain-binding protein and its localization to growth cones of cultured neurons.

Cortactin is an actin-binding protein that contains several potential signaling motifs including a Src homology 3 (SH3) domain at the distal C terminus. Translocation of cortactin to specific cortical actin structures and hyperphosphorylation of cortactin on tyrosine have been associated with the cortical cytoskeleton reorganization induced by a variety of cellular stimuli. The function of cortactin in these processes is largely unknown in part due to the lack of information about cellular binding partners for cortactin. Here we report the identification of a novel cortactin-binding protein of approximately 180 kDa by yeast two-hybrid interaction screening. The interaction of cortactin with this 180-kDa protein was confirmed by both in vitro and in vivo methods, and the SH3 domain of cortactin was found to direct this interaction. Since this protein represents the first reported natural ligand for the cortactin SH3 domain, we designated it CortBP1 for cortactin-binding protein 1. CortBP1 contains two recognizable sequence motifs within its C-terminal region, including a consensus sequence for cortactin SH3 domain-binding peptides and a sterile alpha motif. Northern and Western blot analysis indicated that CortBP1 is expressed predominately in brain tissue. Immunofluorescence studies revealed colocalization of CortBP1 with cortactin and cortical actin filaments in lamellipodia and membrane ruffles in fibroblasts expressing CortBP1. Colocalization of endogenous CortBP1 and cortactin was also observed in growth cones of developing hippocampal neurons, implicating CortBP1 and cortactin in cytoskeleton reorganization during neurite outgrowth.

3T3 Cells↗

Translocation of cortactin to the cell periphery is mediated by the small GTPase Rac1.

Small GTPases of the Rho family regulate signaling pathways that control actin cytoskeletal structures. In Swiss 3T3 cells, RhoA activation leads to stress fiber and focal adhesion formation, Rac1 to lamellipoda and membrane ruffles, and Cdc42 to microspikes and filopodia. Several downstream molecules mediating these effects have been recently identified. In this report we provide evidence that the intracellular localization of the actin binding protein cortactin, a Src kinase substrate, is regulated by the activation of Rac1. Cortactin redistributes from the cytoplasm into membrane ruffles as a result of growth factor-induced Rac1 activation, and this translocation is blocked by expression of dominant negative Rac1N17. Expression of constitutively active Rac1L61 evoked the translocation of cortactin from cytoplasmic pools into peripheral membrane ruffles. Expression of mutant forms of the serine/threonine kinase PAK1, a downstream effector of Rac1 and Cdc42 recently demonstrated to trigger cortical actin polymerization and membrane ruffling, also led to the translocation of cortactin to the cell cortex, although this was effectively blocked by coexpression of Rac1N17. Collectively these data provide evidence for cortactin as a putative target of Rac1-induced signal transduction events involved in membrane ruffling and lamellipodia formation.

3T3 Cells↗

Altered fractionation in radiation therapy for squamous-cell carcinoma of the head and neck.

Following is a review of altered fractionation in radiation therapy for head and neck cancer. The goals of altered fractionation are to increase local-regional control and/or reduce the risk of late complications. Altered fractionation schedules can be broadly classified as accelerated fractionation and hyperfractionation. Data indicate that some of these schedules, particularly hyperfractionated radiation therapy, offer improved results compared to conventionally fractionated radiation therapy. Most investigators have observed no significant increased risk of late complications with the dose-fractionation schedules described.

Carcinoma, Squamous Cell↗

CT findings in chondroradionecrosis of the larynx.

PURPOSE: Our goal was to describe the CT findings before and after radiation therapy in a series of patients with laryngeal chondroradionecrosis. METHODS: The CT studies obtained before and after radiation therapy in nine patients with the diagnosis of laryngeal chondroradionecrosis were reviewed retrospectively. RESULTS: CT scans revealed abnormalities in all patients. A variable degree of laryngeal soft-tissue swelling was seen in eight of the patients. In four patients, cartilaginous abnormalities were visible initially, and appeared in three of four other patients who had further follow-up CT studies. Six patients had involvement of the thyroid cartilage; collapse of the thyroid cartilage was seen in two cases and gas bubbles were visible adjacent to the thyroid cartilage in three cases. Four patients with involvement of the thyroid cartilage eventually underwent total laryngectomy, and one died suddenly in severe respiratory distress. In all three patients with arytenoidal involvement, anterior dislocation of this cartilage was seen; in two of these patients, the adjacent part of the cricoid cartilage showed some sclerosis. Two patients with arytenoidal necrosis (both with cricoidal sclerosis) kept a functional larynx. In one case, cricoidal sclerosis was seen in association with lysis of the thyroid cartilage. CONCLUSION: The CT appearance of laryngeal chondroradionecrosis is nonspecific, but the diagnosis can be strongly suggested in cases of sloughing of the arytenoid cartilage, fragmentation and collapse of the thyroid cartilage, and/or in the presence of gas bubbles around the cartilage.

Adult↗

Induction of apoptosis after expression of PYK2, a tyrosine kinase structurally related to focal adhesion kinase.

Many cells (e.g., epithelial cells) require attachment to the extracellular matrix (ECM) to survive, a phenomenon known as anchorage-dependent cell survival. Disruption of the cell-ECM interactions mediated by the integrin receptors results in apoptosis. Focal adhesion kinase (FAK), a 125-kD protein tyrosine kinase activated by integrin engagement, appears to be involved in mediating cell attachment and survival. Proline-rich tyrosine kinase 2 (PYK2), also known as cellular adhesion kinase beta (CAKbeta) and related adhesion focal tyrosine kinase, is a second member of the FAK subfamily and is activated by an increase in intracellular calcium levels, or treatment with TNFalpha and UV light. However, the function of PYK2 remains largely unknown. In this study, we show that over-expression of PYK2, but not FAK, in rat and mouse fibroblasts leads to apoptotic cell death. Using a series of deletion mutants and chimeric fusion proteins of PYK2/FAK, we determined that the NH2-terminal domain and tyrosine kinase activity of PYK2 were required for the efficient induction of apoptosis. Furthermore, the apoptosis mediated by PYK2 could be suppressed by over-expressing catalytically active v-Src, c-Src, phosphatidylinositol-3-kinase, or Akt/protein kinase B. In addition, it could also be suppressed by overexpressing an ICE or ICE-like proteinase inhibitor, crmA, but not Bcl2. Collectively, our results suggest that PYK2 and FAK, albeit highly homologous in primary structure, appear to have different functions; FAK is required for cell survival, whereas PYK2 induces apoptosis in fibroblasts.

Animals↗

An analysis of factors influencing the outcome of postoperative irradiation for squamous cell carcinoma of the oral cavity.

PURPOSE: To analyze factors influencing outcome in patients who received postoperative irradiation for advanced squamous cell carcinoma of the oral cavity. METHODS AND MATERIALS: Between October 1964 and November 1993, 134 patients with 135 previously untreated primary invasive squamous cell carcinomas of the oral cavity (excluding the lip) were treated postoperatively with continuous courses of external-beam irradiation at the University of Florida. All patients had a minimum follow-up of 2 years (analysis, December 1995). No patient was lost to follow-up. RESULTS: The 10-year actuarial rates of primary site, neck, and local-regional control were 79%, 88%, and 71%, respectively. Recurrence of cancer above the clavicles developed in 35 patients. Ninety-four percent of the recurrences were within the primary field of irradiation (anterior to the plane of the spinal cord); there were 24 recurrences at the primary site and nine in the upper neck alone. There were no failures in the neck area behind the plane of the spinal cord (i.e., the "posterior strip"). Two failures occurred in the low neck below the level of the thyroid notch. In univariate analyses, factors that affected local-regional control included pathologic stage (I-II vs. III-IV, p = 0.04), margin status (invasive cancer at the margin vs. other, p = 0.0007), multifocal tumor (p = 0.05), perineural invasion (p = 0.04), and number of indications for postoperative irradiation (p = 0.05). Extracapsular nodal extension was marginally significant (p = 0.07). In multivariate analysis, positive margins and number of indications remained significant. These factors were used to define relatively favorable (< 4 indications, margins not positive) and unfavorable (> or = 4 indications and/or margins positive for invasive cancer) groups. For both favorable and unfavorable groups, there were nonsignificant trends toward improved local-regional control for patients who began irradiation within 45-50 days, compared with those whose irradiation began later. There were also nonsignificant trends toward improved control for patients treated with shorter overall irradiation treatment courses. An analysis was also performed on the effects of duration of the overall "treatment package" (from the date of surgery until the last day of irradiation). For patients with unfavorable tumors, there was a significantly higher probability of local-regional control for patients whose overall "treatment package" was < or = 100 days (60% vs. 14%, p = 0.04). The 5-year rate of distant metastasis as the sole site of failure was 8% and was predicted by pathologic N stage (N0-N1, 3%; N2-N3, 16%, p = 0.02), as well as the presence (20%) or absence (6%) of extracapsular nodal extension (p = 0.06). The 5-year freedom-from-relapse rate was 63%. The 5-year survival and cause-specific survival rates were 50% and 67%, respectively. Four severe radiation injuries occurred (3%). CONCLUSION: This paper provides data that define relatively favorable and unfavorable groups of patients in the postoperative setting. Patients with four or more indications for irradiation and/or invasive cancer at the surgical margins have a worse outcome than patients who do not have these negative factors; this is true in spite of the fact that the unfavorable group received higher doses of radiation. Attention should be focused on not only the interval between surgery and irradiation, but also time-dose parameters and the overall duration of the treatment "package."

Adolescent↗

Can pretreatment computed tomography predict local control in T3 squamous cell carcinoma of the glottic larynx treated with definitive radiotherapy?

PURPOSE: To determine if pretreatment computed tomography (CT) can predict local control in T3 squamous cell carcinoma of the glottic larynx treated with definitive radiotherapy (RT). METHODS AND MATERIALS: Forty-two patients with previously untreated T3 squamous cell carcinoma of the glottic larynx were treated for cure with RT alone; all had a minimum 2-year follow-up. Tumor volumes and extent were determined by consensus of two head and neck radiologists on pretreatment CT studies. A tumor score was calculated and assigned to each primary lesion depending on the extent of laryngeal spread. Sclerosis of any laryngeal cartilage was recorded. The specific CT parameters assessed were correlated with local control. RESULTS: Tumor volume was a significant predictor of local control. For tumors measuring < 3.5 cm3, local control was achieved in 22 of 26 patients (85%), whereas for tumors > or = 3.5 cm3, local control was achieved in 4 of 16 patients (25%) (p = 0.0002). Sensitivity and specificity using this cutpoint were 85% and 75%, respectively. Tumor score as a measure of anatomic extent was also found to be a significant predictor of local control. The local control rate for tumors assigned a low tumor score (< or = 5) was 78% (21 of 27) compared to 33% (5 of 15) for tumors assigned a high tumor score (6, 7, or 8) (p = 0.008). A significant decrease in the local control rate was observed for cancers involving the paraglottic space at the false vocal cord level (14 of 16 [88%] vs. 12/26 [46%]) (p = 0.010), cancers involving the face of the arytenoid (15 of 18 [83%] vs. 11 of 24 [46%]) (p = 0.024), and tumors involving the interarytenoid region (25 of 36 [69%] vs. 1 of 6 [17%]; p = 0.020). There were 12 patients with sclerosis of both the ipsilateral arytenoid and the adjacent cricoid cartilage. These patients showed a significant decrease in local control (4 of 12 [33%]). CONCLUSION: Pretreatment CT can stratify patients with T3 glottic carcinoma into groups more or less likely to be locally controlled with definitive RT. The local control rate for these tumors can be improved using a CT-based tumor profile; the ideal CT profile for a radiocurable T3 glottic larynx carcinoma is volume < 3.5 cm3 and no or single laryngeal cartilage sclerosis.

Carcinoma, Squamous Cell↗

Postoperative radiation of open head and neck wounds--updated.

BACKGROUND: Postoperative radiotherapy is commonly used in treating head and neck cancer. A concern is the possibility of an unhealed surgical wound delaying or disrupting the treatment schedule. Our institution previously reported our experience on the outcome of radiotherapy on unhealed wounds from 1977 to 1984. METHODS: In an effort to update and enlarge this series, we reviewed the charts of patients receiving postoperative radiotherapy from 1985 to 1990. Of 267 patients, 20 had unhealed wounds or fistulas at the beginning of treatment. The wounds healed spontaneously in 17 of these patients, 1 required surgical closure, and 2 never healed. Combining our current and previous series, 452 patients had onset of postoperative radiation therapy at our institution from 1977 through 1990, of whom 33 had unhealed wounds at the onset of irradiation. RESULTS: In 22 of 33 (67%) patients, the wounds healed spontaneously (mean: 98 days, range: 36 to 304 days). Five additional patients achieved successful wound healing following surgical closure (mean: 281 days, range; 112 to 608 days). The remaining 6 patients died before healing was complete (4 patients) or were lost to follow-up (2 patients) at 16 and 27 months before wound healing occurred. Nine patients in this study are alive with no evidence of disease, 19 died of cancer, and 5 died of other causes. CONCLUSIONS: When there are indications to deliver irradiation in the postoperative setting, it is desirable to initiate treatment within 6 weeks of the data of surgery. Although it is preferable to have completely closed operative wounds prior to irradiation, some consideration must be given to initiating irradiation in the face of incompletely closed wounds when it is anticipated that healing time will be prolonged. In some patients, the wounds continue to heal during the course of irradiation, or will stabilize, and can be surgically managed after irradiation is completed or may spontaneously heal after treatment. Excessive delays in initiating appropriate cancer therapy may lead to recurrence prior to irradiation; such recurrences are rarely successfully salvaged.

Adult↗

Late adolescent risk-taking: effects of perceived benefits and perceived risks on behavioral intentions and behavioral change.

To assess the predictive utility of perceived benefits and risks of risk-taking behaviors (RTBs) on behavioral intentions and behavioral change, data were collected from 187 male and female late adolescent college students (ages 17-20). Perceived benefits, perceived risks, behavioral intentions, and involvement for 18 RTBs were assessed at T1 and T2 (3 months later). Factor analyses were performed on T1 involvement data, and six RTB factors emerged: Alcohol RTBs, Illegal Drug RTBs, Stereotypic Male RTBs, Social RTBs, Sex RTBs, and Imprudent RTBs. Regression analyses indicated that perceived benefits accounted for significant variance in behavioral intentions for each of the six factors and Overall RTB; perceived risks accounted for significant variance in behavioral intentions for five of the factors. Similar regression analyses indicated that perceived benefits accounted for significant variance in behavior change (over a 3 month period) for each of the six factors and the Overall RTB score, whereas perceived risks accounted for significant variance for only one factor (Illegal Drug RTBs). The result suggest that, among late adolescents, perceived benefits are better determinants of behavior change for RTBs than are perceived risks. Both perceived benefits and perceived risks, however, are important determinants of behavioral intentions. These findings support previous work identifying adolescents as "sensation seekers". Interventions should address perceived benefits of RTB, rather than relying solely on promoting knowledge of the risks. Assessment of adolescent RTB should continue to use multi-item measures to obtain a broad picture of the variety of behaviors commonly endorsed by adolescents.

Adaptation, Psychological↗

Sexual behavior of HIV-seropositive young men with congenital coagulopathies. Hemophilia Behavioral Intervention Projects (HBIEP) Study Group.

PURPOSE: To describe the self-reported sexual behaviors of human immunodeficiency virus (HIV)-seropositive youths with congenital coagulopathies in order to guide the development of interventions to prevent secondary transmission. SUBJECTS: A total of 297 HIV-seropositive males, 12-24 years of age, were sampled from 11 hemophilia treatment centers and 28 affiliated subsites. METHODS: Review of clinical records and self-administered survey of HIV-related knowledge, attitudes and behaviors. Subjects were classified and compared by self-reported sexual behavior over the lifetime and the prior 6 months into five mutually exclusive groups (G1-5). RESULTS: A total of 42% of subjects were virgins who never had oral, vaginal, or rectal sex (G1); 10% were nonvirgins who had abstained (G2); 13% were virgins and nonvirgins who had intimate touch only (G3); 21% had intercourse and always used condoms (G4); and 13% had had unsafe intercourse (G5). Among the groups, G5 was the oldest, least likely to forego sex, most angry and anxious when reminded of HIV, and most reluctant to disclose serostatus to friends. CONCLUSIONS: Most subjects (87%) had safer sex or abstained in the last 6 months. A relatively small group of HIV-seropositive youth with bleeding disorders were engaged in unprotected intercourse and in need of intensive help with HIV risk reduction.

Adolescent↗

Ischemia-induced inhibition of calcium uptake into rat brain microsomes mediated by Mg2+/Ca2+ ATPase.

It is well established that ischemia is associated with prolonged increases in neuronal intracellular free calcium levels. Recent data suggest that regulation of calcium uptake and release from the endoplasmic reticulum is important in maintaining calcium homeostasis. The endoplasmic reticulum Mg2+/Ca2+ ATPase is the major mechanism for sequestering calcium in this organelle. Inhibition of this enzyme may play a causal role in the loss of calcium homeostasis. In order to investigate the effect of ischemia on calcium sequestration into the endoplasmic reticulum, microsomes were isolated from control and ischemic whole brain homogenates by differential centrifugation. Calcium uptake was measured by radioactive calcium (45Ca2+) accumulation in the microsomes mediated by Mg2+/Ca2+ ATPase. Ischemia caused a statistically significant inhibition of presteady-state and steady-state calcium uptake. Duration of ischemia was directly proportional to the degree of inhibition. Decreased calcium uptake was shown not to be the result of increased calcium release from ischemic compared with control microsomes nor the results of selective isolation of ischemic microsomes from the homogenate with a decreased capacity for calcium uptake. The data demonstrate that ischemia inhibits the ability of brain microsomes to sequester calcium and suggest that loss of calcium homeostasis is due, in part, to ischemia-induced inhibition of endoplasmic reticulum Mg2+/Ca2+ ATPase.

Adenosine Triphosphate↗