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Biomedical subjects

J L Freeman

Publications and source records attributed to J L Freeman.

At least 37 records · Page 2Linked to original sources
PubMed2000

Epstein Barr virus genome in nasopharyngeal carcinomas from New Zealand.

BACKGROUND: The population in New Zealand is a heterogeneous mix of Caucasians (80%), Maori (9%), and Polynesians (10%). It is believed that the Polynesians are of Chinese descent and may harbor the same high incidence of nasopharyngeal carcinoma (NPC). In addition, it is not known whether the Epstein-Barr virus (EBV) is as closely associated with the development of NPC in Polynesians as it is in those of Chinese origin. METHODS: This study reexamines the associative correlation between EBV and NPC with two methods of genetic detection, polymerase chain reaction (PCR) and in-situ hybridization (ISH). In addition, geographic heterogeneity was analyzed to determine whether there are differences in the prevalence of EBV in NPCs among the ethnic mixed populations found in New Zealand. Nasopharyngeal biopsy specimens from 20 patients with NPC and 36 controls were obtained from Auckland. RESULTS: With PCR, EBNA-1, a genomic sequence of EBV in NPC samples was able to be detected with 76.5% sensitivity and 96.7% specificity. By use of ISH, EBV was detected in NPC tissue with 82.4% sensitivity and 100% specificity. CONCLUSION: There seems to be no geoanthropologic differences in terms of the association of EBV with NPC.

Asian People↗
PubMed2000

Prevalence of arthritis in older Mexican Americans.

OBJECTIVE: This study examines the prevalence of self-reported physician-diagnosed arthritis and arthritis symptoms and their relationship to functional limitations in Mexican American elderly. METHODS: We conducted a cross-sectional study using a probability sample of 2,873 non-institutionalized Mexican American men and women aged 65 or older, residing in the southwestern United States. Measures included self-reported physician-diagnosed arthritis, morning pain or stiffness, pain when standing, global health rating, activities of daily living (ADL), instrumental activities of daily living (IADL), depressive symptoms, presence of chronic diseases (diabetes mellitus, hypertension, heart attack, stroke), and body mass index. The Mantel-Haenszel chi-square statistic was used to test differences by arthritis status, and a logistic regression model was used to predict the odds of having arthritis. RESULTS: The overall prevalence of self-reported physician-diagnosed arthritis in the sample was 40.8 percent, 50.0 percent among women and 28.8 percent among men (P < 0.001). Morning pain or stiffness was reported by 37.7 percent of respondents and pain when standing or walking by 31.9 percent. All comorbid conditions, and both IADL and ADL limitations, were more prevalent in those with arthritis than in those without arthritis. Female sex and several medical conditions were independently associated with self-reported arthritis. CONCLUSIONS: Self-reported physician-diagnosed arthritis is common among older Mexican Americans. Functional limitation and disability are more prevalent among subjects with arthritis than among those without arthritis.

Activities of Daily Living↗
PubMed2000

An approach to identifying incident breast cancer cases using Medicare claims data.

This study developed and evaluated a method for ascertaining a newly diagnosed breast cancer case using multiple sources of data from the Medicare claims system. Predictors of an incident case were operationally defined as codes for breast cancer-related diagnoses and procedures from hospital inpatient, hospital outpatient, and physician claims. The optimal combination of predictors was then determined from a logistic regression model using 1992 data from the linked SEER registries-Medicare claims data base and a sample of noncancer controls drawn from the SEER areas. While the ROC curve demonstrates that the model can produce levels of sensitivity and specificity above 90%, the positive predictive value is comparatively low (67-70%). This low predictive value is largely the result of the model's limitation in distinguishing recurrent and secondary malignancies from incident cases and possibly from the model identifying true incident cases not identified by SEER. Nevertheless, the logistic regression approach is a useful method for ascertaining incident cases because it allows for greater flexibility in changing the performance characteristics by selecting different cut-points depending on the application (e.g., high sensitivity for registry validation, high specificity for outcomes research). It also allows us to make specific adjustments to population based estimates of breast cancer incidence with claims.

Aged↗
PubMed2000

PANAL: an integrated resource for Protein sequence ANALysis.

SUMMARY: We present PANAL, an integrated resource for protein sequence analysis. The tool allows the user to simultaneously search a protein sequence for motifs from several databases, and to view the result as an intuitive graphical summary.

Computational Biology↗
PubMed2000

Accuracy and completeness of Medicare claims data for surgical treatment of breast cancer.

BACKGROUND: Although a number of studies have used Medicare claims data to study trends and variations in breast cancer treatment, the accuracy and completeness of information on surgical treatment for breast cancer in the Medicare data have not been validated. OBJECTIVES: This study assessed the accuracy and completeness of Medicare claims data for breast cancer surgery to determine whether Medicare claims can serve as a source of data to augment information collected by cancer registries. METHODS: We used the Surveillance, Epidemiology and End Results (SEER) Cancer Registry-Medicare data and compared Medicare claims on surgery with the surgery recorded by the SEER registries for 23,709 women diagnosed with breast cancer at > or =65 years of age from 1991 through 1993. RESULTS: More than 95% of women having mastectomies according to the Medicare data were confirmed by SEER. For breast-conserving surgery, 91% of cases were confirmed by SEER. The Medicare physician services claims and inpatient claims were approximately equal in accuracy on type of surgery. The Medicare outpatient claims were less accurate for breast-conserving surgery. In terms of completeness, when the 3 claims sources were combined, 94% of patients receiving breast cancer surgery according to SEER were identified by Medicare. CONCLUSIONS: The combined Medicare claims database, which includes the inpatient, outpatient, and physician service claims, provides valid information on surgical treatment among women known to have breast cancer. The claims are a rich source of data to augment the information collected by tumor registries and provide information that can be used to follow long-term outcomes of Medicare beneficiaries.

Breast Neoplasms↗
PubMed2000

Molecular basis off hurthle cell papillary thyroid carcinoma.

Among thyroid neoplasms, Hurthle cell tumors (HCTs) have traditionally been a distinct diagnostic category. Hurthle cell adenomas are encapsulated follicular lesions with benign behavior. Hurthle cell carcinomas exhibit unequivocal capsular and/or vascular invasion; they are aggressive tumors with a poor prognosis. Recently, Hurthle cell papillary thyroid carcinomas (PTCs) have been identified on morphological grounds. We hypothesize that a subset of HCTs represent PTC with clinical, histological, and immunohistochemical features based on specific molecular events. ret/PTC gene rearrangements give rise to novel oncogenes that are unique to PTC. We studied a group (n = 50) of HCTs for ret/PTC gene rearrangements. Tumors were examined for papillary differentiation by light microscopic evaluation of nuclear features, by RT-PCR for ret/PTC gene rearrangements, and by immunohistochemistry for ret. Among 24 noninvasive tumors, 13 contained ribonucleic acid for ret/PTC-1, -2, or -3, and 9 of these were immunoreactive for ret. Among 19 Hurthle cell carcinomas, 15 had focal nuclear hypochromasia with grooves and/or inclusions; expressed transcripts of ret/PTC-1, -2, or-3; and exhibited ret positivity. Tumors with ret/PTC gene rearrangements tended to have lymph node metastases rather than hematogenous spread. Our results indicate that a subset of HCTs exhibit features of PTC that are attributable to specific gene rearrangements, resulting in expression of ret/PTC oncogenes. These data support subclassification of HCTs into three groups: Hurthle cell adenomas, Hurthle cell carcinomas, and Hurthle cell PTC.

Adenocarcinoma, Papillary↗
PubMed2000

Associations among hospital capacity, utilization, and mortality of US Medicare beneficiaries, controlling for sociodemographic factors.

OBJECTIVE: To explore whether geographic variations in Medicare hospital utilization rates are due to differences in local hospital capacity, after controlling for socioeconomic status and disease burden, and to determine whether greater hospital capacity is associated with lower Medicare mortality rates. DATA SOURCES/STUDY SETTING: The study population: a 20 percent sample of 1989 Medicare enrollees. Measures of resources were based on a national small area analysis of 313 Hospital Referral Regions (HRR). Demographic and socioeconomic data were obtained from the 1990 U.S. Census. Measures of local disease burden were developed using Medicare claims files. STUDY DESIGN: The study was a cross-sectional analysis of the relationship between per capita measures of hospital resources in each region and hospital utilization and mortality rates among Medicare enrollees. Regression techniques were used to control for differences in sociodemographic characteristics and disease burden across areas. DATA COLLECTION/EXTRACTION METHODS: Data on the study population were obtained from Medicare enrollment (Denominator File) and hospital claims files (MedPAR) and U.S. Census files. PRINCIPAL FINDINGS: The per capita supply of hospital beds varied by more than twofold across U.S. regions. Residents of areas with more beds were up to 30 percent more likely to be hospitalized, controlling for ecologic measures of socioeconomic characteristics and disease burden. A greater proportion of the population was hospitalized at least once during the year in areas with more beds; death was also more likely to take place in an inpatient setting. All effects were consistent across racial and income groups. Residence in areas with greater levels of hospital resources was not associated with a decreased risk of death. CONCLUSIONS: Residence in areas of greater hospital capacity is associated with substantially increased use of the hospital, even after controlling for socioeconomic characteristics and illness burden. This increased use provides no detectable mortality benefit.

Aged↗
PubMed1999

Feedback inhibition of G protein-coupled receptor kinase 2 (GRK2) activity by extracellular signal-regulated kinases.

G protein-coupled receptor kinase (GRK)-mediated receptor phosphorylation and beta-arrestin binding uncouple G protein-coupled receptors (GPCRs) from their respective G proteins and initiates the process of receptor internalization. In the case of the beta(2)-adrenergic receptor and lysophosphatidic acid receptor, these processes can lead to ERK activation. Here we identify a novel mechanism whereby the activity of GRK2 is regulated by feedback inhibition. GRK2 is demonstrated to be a phosphoprotein in cells. Mass spectrometry and mutational analysis localize the site of phosphorylation on GRK2 to a carboxyl-terminal serine residue (Ser(670)). Phosphorylation at Ser(670) impairs the ability of GRK2 to phosphorylate both soluble and membrane-incorporated receptor substrates and dramatically attenuates Gbetagamma-mediated activation of this enzyme. Ser(670) is located in a peptide sequence that conforms to an ERK consensus phosphorylation sequence, and in vitro, in the presence of heparin, ERK1 phosphorylates GRK2. Inhibition of ERK activity in HEK293 cells potentiates GRK2 activity, whereas, conversely, ERK activation inhibits GRK2 activity. The discovery that ERK phosphorylates and inactivates GRK2 suggests that ERK participates in a feedback regulatory loop. By negatively regulating GRK-mediated receptor phosphorylation, beta-arrestin-mediated processes such as Src recruitment and clathrin-mediated internalization, which are required for GPCR-mediated ERK activation, are inhibited, thus dampening further ERK activation.

Cell Line↗
PubMed1999

Nasopharyngeal brush biopsies and detection of nasopharyngeal cancer in a high-risk population.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is an important tumor in many countries. Ethnic and regional factors strongly influence disease risk. NPC is usually diagnosed late in disease development, and 10-year survival rates are as low as 10%. Epstein-Barr virus (EBV), a possibly causative agent, is present in all cells of essentially all undifferentiated NPCs. We wished to determine the following: 1) whether an ambulatory nasopharyngeal brush biopsy could provide sufficient tumor cell DNA for the detection of EBV and 2) whether the detection of EBV in this locale reflects the presence of tumor cells or simply EBV carrier status. METHODS: We collected nasopharyngeal tissue via ambulatory brush biopsies from 21 patients with newly diagnosed NPC and from 157 subjects with other otolaryngologic complaints. The majority of study subjects were from high-risk populations. Sample DNA was analyzed for the presence of EBV genomic sequences by use of the polymerase chain reaction (PCR). RESULTS: Ninety-six percent of samples yielded sufficient DNA for PCR amplification. Nineteen of 21 patients with NPC brushed positive for EBV DNA, while all but two (1.3%) of 149 informative control subjects were negative for EBV (two-sided P<.0001). One of the EBV-positive control subjects had an EBV-positive inverted sinonasal papilloma; the other EBV-positive control subject exhibited no overt clinical disease. CONCLUSION: Demonstration of EBV DNA in nasopharyngeal brush biopsy specimens detects NPC with a sensitivity of at least 90% (95% confidence interval = 89.63%-91.32%) and a specificity of approximately 99% (95% confidence interval = 98.64%-98.68%). This technique merits further testing as a possible ambulatory screening strategy in high-risk populations.

Adolescent↗
PubMed1999

Supraomohyoid neck dissection. Is it diagnostic or therapeutic?

BACKGROUND: The supraomohyoid neck dissection (SOHND) is often performed in patients with cancer of the oral cavity, where there is no clinical or radiologic evidence of regional metastases. When on pathologic examination positive neck nodes are found, however, some consider it a curative operation, whereas others regard it as a staging procedure only. METHODS: We retrospectively reviewed 43 patients with cancer of the oral cavity who had a SOHND during the period from 1991 to 1994. All patients were staged as having N0 disease and had a total of 48 SOHNDs (38 unilateral, 5 bilateral). The follow-up period was at least 2 years. RESULTS: Seven of 48 N0-staged necks showed occult metastasis (15%). Two of these patients received postoperative radiotherapy. One of 7 (14%) patients with pathologic node-positive disease on the SOHND side developed recurrent ipsilateral neck disease during the follow-up period, whereas 4 (10%) recurrences developed in 41 necks that were pathologically staged as N0. Survival was 88% for patients with pathologically N0 necks versus 86% for patients with pathologically N+; disease. CONCLUSION: Supraomohyoid neck dissection is an effective staging procedure; however, in this group of patients, neck recurrence and patient survival after SOHND appear not to be related to pathology N stage. Also, SOHND with or without adjuvant radiotherapy appears to control the neck in the majority of patients, attesting to therapeutic efficacy. A prospective study is needed, however, to see if a "wait and see" policy does not achieve similar long-term outcome.

Head and Neck Neoplasms↗
PubMed1999

Information on radiation treatment in patients with breast cancer: the advantages of the linked medicare and SEER data. Surveillance, Epidemiology and End Results.

Several studies have found underutilization of radiotherapy in patients with breast cancer; but there are concerns about the completeness of various databases on radiotherapy. We used the linked Medicare-SEER (Surveillance, Epidemiology and End Results) database to compare information on receipt of radiotherapy after diagnosis of breast cancer. More than 18% of women identified by Medicare data as receiving radiotherapy were not so identified by SEER, and 7% of those identified as receiving radiotherapy by SEER were not identified by Medicare. Risk of discordance on radiotherapy information between the two data sets was especially high in women receiving breast-conserving surgery. The combined SEER-Medicare database gives a more complete picture on the use of radiotherapy. The previously reported geographic variations in the use of radiotherapy for breast cancer may be due in part to underreporting of radiotherapy in some areas.

Adult↗
PubMed1999

The declining use of axillary dissection in patients with early stage breast cancer.

OBJECTIVES: To determine any changes in usage of axillary dissection over time from 1983 to 1993, and to characterize those patients who do not receive axillary node dissection. METHODS: A total of 129,946 female patients receiving cancer-directed surgery for early stage breast cancer, who were identified from the SEER (Surveillance, Epidemiology and End Results) program and diagnosed from 1983 to 1993, were included in the study. The surgical treatment and axillary dissection were based on treatment data collected by the SEER during the first course of therapy. Logistic regression analyses were used to assess the effect of patient and tumor characteristics on the likelihood of not receiving different types of treatment. RESULTS: The percentage of women not receiving axillary dissection has increased over time, from 14.4% in 1983 to 16.8% in 1993. Nearly a quarter of women undergoing breast conserving surgery for local stage breast cancer receive neither axillary dissection nor radiotherapy. Older, unmarried, and non-white women and those with very small (< 0.5 cm) or very large (> or = 4 cm) tumors were most likely to receive neither axillary node dissection nor irradiation. Among those not receiving axillary dissection, 42% had tumors 1-3 cm in size and were not receiving radiation therapy. CONCLUSIONS: There is an apparent divergence between the type of patient who has been recommended as an appropriate candidate for avoiding axillary dissection (those with small tumors and those who will receive adjuvant therapy) and those who are actually not receiving axillary dissection in the community.

Adult↗
PubMed1999

Temporal and regional variation in the use of breast-conserving surgery and radiotherapy for older women with early-stage breast cancer from 1983 to 1995.

BACKGROUND: Authorities recommend radiation therapy after breast-conserving surgery for breast cancer. Numerous studies have reported that older women diagnosed with breast cancer are less likely to receive radiation after breast-conserving surgery. It is unclear how care of older women with breast cancer has changed over time. METHODS: Women with local or regional stage breast cancer diagnosed between 1983-1995 were identified from the Surveillance, Epidemiology, and End Results (SEER) Cancer Registries. The treatment information in SEER includes type of surgical procedures and receipt of radiation therapy. RESULTS: There were small increases in the percentage of women receiving breast-conserving surgery during the 1980s followed by substantial increases in the 1990s. Age was a major factor in determining receipt of radiation therapy after breast-conserving surgery. A large increase in use of radiotherapy after surgery was observed in women aged > or = 75, from below 30% in 1983 to over 50% in 1995. Women aged > or = 75 diagnosed in 1992-1995 were 1.76 and 2.34 times more likely to receive radiation for local and regional stage respectively, as compared to those in 1983-1987. There was no increase in use of radiation for women aged < 65. CONCLUSIONS: There has been a substantial increase in use of breast-conserving surgery and in receipt of radiation therapy after breast-conserving surgery in older women. However, there was a net increase in the percentage of all women with breast cancer who received this surgery without radiotherapy, due to the large increase in the overall percentage of women receiving this surgery.

Aged↗
PubMed1999

Oncogene profile of papillary thyroid carcinoma.

BACKGROUND: Our purpose was to study the expression of multiple oncogenes in papillary thyroid cancer for possible interactions and prognostic significance. METHODS: Twenty papillary thyroid carcinomas were studied for expression/mutation of 3 oncogenes: ras, ret/PTC, and erbB-2/neu. H, N, and K ras codons were examined by polymerase chain reaction (PCR), single-stranded conformation polymorphism, and sequencing. The thyroid oncogene ret/PTC was identified by reverse transcription (RT)-PCR. Gene amplification of erbB-2/neu was analyzed by differential PCR. The transmembrane domain of erbB-2/neu was sequenced for activating mutations. Quantitation of erbB-2/neu mRNA was evaluated by competitive RT-PCR, and protein expression was determined by immunohistochemistry. RESULTS: Among 20 tumors, 3 had insular/anaplastic dedifferentiation, 13 were intrathyroidal, and 7 were metastatic to cervical lymph nodes (6) or lung (1). An H-ras 13 mutation was found in 1 metastatic tumor and an N-ras 61 mutation in 1 intrathyroidal tumor. ret/PTC was identified in 3 intrathyroidal and 5 metastatic tumors. No erbB-2/neu DNA amplification or mutations were identified, although 4 tumors had elevated erbB-2/neu mRNA levels. Three of 20 patients had abnormalities detected in multiple oncogenes; 2 had elevated erbB-2/neu mRNA and ret/PTC rearrangements, and 1 of these had pulmonary metastasis. An intrathyroidal papillary cancer had an N61 ras mutation and a ret/PTC gene rearrangement. CONCLUSIONS: ret/PTC rearrangements are present in 40% of papillary thyroid carcinomas and may play a role in metastatic behavior. In contrast, ras mutations are rare (10%). erbB-2/neu gene amplification and activating mutations are not detected, although elevated mRNA levels were found in 20% of papillary carcinomas. The lack of correlation among the 3 oncogenes in 17 of 20 (85%) papillary thyroid carcinomas suggests that they were not cumulative factors in the pathogenesis of these tumors.

Adult↗
PubMed1998

beta2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein.

G protein-coupled receptor activation leads to the membrane recruitment and activation of G protein-coupled receptor kinases, which phosphorylate receptors and lead to their inactivation. We have identified a novel G protein-coupled receptor kinase-interacting protein, GIT1, that is a GTPase-activating protein (GAP) for the ADP ribosylation factor (ARF) family of small GTP-binding proteins. Overexpression of GIT1 leads to reduced beta2-adrenergic receptor signaling and increased receptor phosphorylation, which result from reduced receptor internalization and resensitization. These cellular effects of GIT1 require its intact ARF GAP activity and do not reflect regulation of GRK kinase activity. These results suggest an essential role for ARF proteins in regulating beta2-adrenergic receptor endocytosis. Moreover, they provide a mechanism for integration of receptor activation and endocytosis through regulation of ARF protein activation by GRK-mediated recruitment of the GIT1 ARF GAP to the plasma membrane.

ADP-Ribosylation Factors↗
PubMed1998

Regulation of G protein-coupled receptor kinase 5 (GRK5) by actin.

G protein-coupled receptor kinases (GRKs) initiate pathways leading to the desensitization of agonist-occupied G-protein-coupled receptors (GPCRs). Here we report that the cytoskeletal protein actin binds and inhibits GRK5. Actin inhibits the kinase activity directly, reducing GRK5-mediated phosphorylation of both membrane-bound GPCRs and soluble substrates. GRK5 binds actin monomers with a Kd of 0.6 microM and actin filaments with a Kd of 0. 2 microM. Mutation of 6 amino acids near the amino terminus of GRK5 eliminates actin-mediated inhibition of GRK5. Calmodulin has previously been shown to bind to the amino terminus of GRK5 (Pronin, A. N., and Benovic, J. L. (1997) J. Biol. Chem. 272, 3806-3812) and here we show calmodulin displaces GRK5 from actin. Calmodulin inhibits GRK5-mediated phosphorylation of GPCRs, but not soluble substrates such as casein. Thus in the presence of actin, calmodulin determines the substrate specificity of GRK5 by preferentially allowing phosphorylation of soluble substrates over membrane-bound substrates.

Actins↗