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Biomedical subjects

J L Freeman

Publications and source records attributed to J L Freeman.

At least 19 recordsLinked to original sources
PubMed2006

Array-based comparative genomic hybridization and copy number variation in cancer research.

Array-based comparative genomic hybridization (aCGH) is a molecular cytogenetic technique used in detecting and mapping DNA copy number alterations. aCGH is able to interrogate the entire genome at a previously unattainable, high resolution and has directly led to the recent appreciation of a novel class of genomic variation: copy number variation (CNV) in mammalian genomes. All forms of DNA variation/polymorphism are important for studying the basis of phenotypic diversity among individuals. CNV research is still at its infancy, requiring careful collation and annotation of accumulating CNV data that will undoubtedly be useful for accurate interpretation of genomic imbalances identified during cancer research.

Animals↗
PubMed2005

Localization of repetitive DNA sequences on in vitro Xenopus laevis chromosomes by primed in situ labeling (PRINS).

Xenopus laevis is an important reference model organism used in many vertebrate studies. Gene mapping in X. laevis, in comparison to other reference organisms, is in its early stages. Few studies have been conducted to localize DNA sequences on X. laevis chromosomes. Primed in situ labeling (PRINS) is a recently developed innovative tool that has been used to locate specific DNA sequences in various organisms. PRINS has been reported to have increased sensitivity compared to other in situ hybridization techniques. In the present study, PRINS was first used to label the location of telomeres at the ends of in vitro X. laevis chromosomes. The terminal location was as expected from in vivo reports, however, the overall amount seemed to decrease in the in vitro chromosomes. Once the PRINS technique was optimized, this technique was used to determine the chromosomal location of the satellite 1 repetitive sequence, which is an important sequence in X. laevis development. The sequence was observed on the interstitial regions of the majority of the chromosomes similar to the in vivo locations reported. In contrast to the telomeric sequence, the amount of sequence appeared to increase in the satellite 1 sequence. PRINS was found to be useful in the localization of repetitive DNA sequences in the X. laevis genome.

Animals↗
PubMed2004

In vivo genotoxicity of atrazine to anuran larvae.

Atrazine has been an environmental contaminant for more than two decades. While there can be little dispute as to the presence of atrazine in non-target watersheds, the debate has centered on the consequences of this contamination. The purpose of this study was to determine if atrazine is genotoxic to developing anurans. Anurans are one of the groups that have the highest potential for being affected by watershed contamination. In initial studies, larvae from two anuran species were exposed to known genotoxic agents. Upon flow cytometric analysis, those organisms exposed to the genotoxic agents resulted in a statistically significant increase in nuclear heterogeneity. Having demonstrated that flow cytometric analysis could be used to detect genotoxicity in anuran larvae, the larvae of the two species were exposed to different levels of atrazine for various durations. The concentrations and lengths of exposure were consistent (albeit on the higher side) with conditions found in the Midwestern US. In neither species was an increase in nuclear heterogeneity observed. Thus, atrazine at levels and time of exposure representing conditions found contaminating Midwestern watersheds does not appear to be genotoxic to developing anurans.

Animals↗
PubMed2003

Generalized epilepsy in hypothalamic hamartoma: evolution and postoperative resolution.

OBJECTIVE: To better understand the epileptogenesis of symptomatic generalized epilepsy in patients with hypothalamic hamartoma and intractable epilepsy, many of whom experience remission of generalized seizures and slow spike-wave discharges following surgery. METHODS: The authors documented the evolution of symptomatic generalized epilepsy in 12 of 20 children who underwent transcallosal microsurgical hypothalamic hamartoma resection. In seven patients they recorded intraoperative EEG from the hamartoma and simultaneously from the scalp and frontal cortex before, during, and after resection. RESULTS: Gelastic seizures began on average at 6 months of age (range birth to 3 years); tonic seizures began at 6 years (range 2 months to 9 years). Normal EEG were reported in early childhood; thereafter, abnormalities were progressive. Interictal spike-wave was recorded intraoperatively over the scalp and cortex in six patients, but not from the hypothalamic hamartoma. Hamartoma resection had no immediate effect on cortical spike-wave, but waking spike-wave was absent in seven patients on subsequent postoperative EEG. Tonic seizures ceased in 11 of 12 patients, but 6 of these had postoperative generalized seizures that resolved over 1 to 6 months. CONCLUSION: Gelastic seizures in hypothalamic hamartoma arise from the hamartoma itself; the interictal spike-wave does not. The evolution of EEG abnormalities, the development of generalized seizures years after onset of gelastic seizures, and the postoperative running down of interictal spike-wave and generalized seizures in these patients may reflect secondary epileptogenesis.

Child↗
PubMed2003

Three-week thyroxine withdrawal thyroglobulin stimulation screening test to detect low-risk residual/recurrent well-differentiated thyroid carcinoma.

Measurement of serum TSH-stimulated thyroglobulin (Tg) is recognized as a sensitive method for detecting residual/recurrent well-differentiated thyroid carcinoma (WDTC) in patients previously treated by surgery and radioactive iodine (RAI) ablation therapy. WDTC patients who have an undetectable serum Tg on thyroid hormone therapy (THT) in the absence of Tg-antibody interference are considered to be at low risk for residual/recurrent disease. Traditional management has been to withdraw T4 for 4-6 weeks or T3 for 2 weeks to stimulate endogenous TSH. However, this prolonged THT withdrawal induces hypothyroidism and its concomitant morbidity. In the present study, we assess the efficacy of shortening the time of T4 withdrawal to only 3 weeks for detecting residual/recurrent WDTC as a sufficient serum TSH stimulus for obtaining a positive serum Tg result without a routine diagnostic whole body scan (WBS). Additionally, we have evaluated the impact of such a T4 withdrawal interval on quality of life and loss of employment time. A total of 181 patients with WDTC selected for study had previously been treated with a bilateral surgical thyroidectomy followed by RAI ablation therapy (average post-surgery to follow-up interval of 10.8 yr). All of the cohort had an undetectable (< 1 microg/l) serum Tg on THT without Tg-antibody interference. Serum TSH and Tg were measured before and after cessation of T4 therapy for 3 weeks. A serum Tg > or = 2 microg/l was considered positive for residual/recurrent disease. A quality of life questionnaire [Short-Form 36 (SF-36)] was administered before withdrawal, at peak TSH and after resumption of therapy. From the completed SF-36 questionnaires, the overall degree of functional impairment was not severe and did not result in loss of employment time. Moreover, this protocol identified three possible responses to the 3-week T4 withdrawal interval as follows: a) serum Tg undetectable with TSH > or = 25 mIU/l (approximately 75% of total cohort); b) serum Tg > or = 2 microg/l (approximately 10% of total cohort) which will require further investigation and treatment for residual/recurrent disease; c) undetectable serum Tg with inadequate TSH rise (approximately 15% of total cohort), which will require TSH stimulation by either longer T4 withdrawal or recombinant human TSH to exclude residual disease. We conclude that a stimulated serum Tg test performed 3 weeks after T4 withdrawal is a simple and cost-effective first-line screening test with minimal morbidity which is sufficient to evaluate low-risk WDTC patients for recurrent/residual carcinoma.

Adenocarcinoma, Follicular↗
PubMed2001

The MetaFam Server: a comprehensive protein family resource.

MetaFam is a comprehensive relational database of protein family information. This web-accessible resource integrates data from several primary sequence and secondary protein family databases. By pooling together the information from these disparate sources, MetaFam is able to provide the most complete protein family sets available. Users are able to explore the interrelationships among these primary and secondary databases using a powerful graphical visualization tool, MetaFamView. Additionally, users can identify corresponding sequence entries among the sequence databases, obtain a quick summary of corresponding families (and their sequence members) among the family databases, and even attempt to classify their own unassigned sequences. Hypertext links to the appropriate source databases are provided at every level of navigation. Global family database statistics and information are also provided. Public access to the data is available at http://metafam.ahc.umn.edu/.

Computational Biology↗
PubMed2001

Immunohistochemical diagnosis of papillary thyroid carcinoma.

In thyroid, the diagnosis of papillary carcinoma (PC) is based on nuclear features; however, identification of these features is inconsistent and controversial. Proposed markers of PC include HBME-1, specific cytokeratins (CK) such as CK19, and ret, the latter reflecting a ret/PTC rearrangement. We applied immunohistochemical stains to determine the diagnostic accuracy of these three markers. Formalin-fixed, paraffin-embedded tissue from 232 surgically resected thyroid nodules included 40 hyperplastic nodules (NH), 35 follicular adenomas (FA), 138 papillary carcinomas (PC; 54 classical papillary tumors and 84 follicular variant papillary carcinomas [FVPC]), 4 follicular carcinomas (FC), 6 insular carcinomas (IC), 7 Hürthle cell carcinomas (HCC), and 2 anaplastic carcinomas (AC). HBME-1 and ret were negative in all NH and FA; some of these exhibited focal CK19 reactivity in areas of degeneration. Half of the FC and AC exhibited HBME-1 staining but no positivity for CK19 or ret. In PC, 20% of cases stained for all three markers. Classical PC had the highest positivity with staining for HBME-1 in 70%, CK19 in 80%, and ret in 78%. FVPC were positive for HBME-1 in 45%, for CK19 in 57%, and for ret in 63%; only 7 FVPC were negative for all three markers. The six IC exhibited 67% staining for HBME-1 and 50% positivity for CK19 and ret. The seven HCC had 29% positivity for HBME-1 and CK19, and 57% positivity for ret. This panel of three immunohistochemical markers provides a useful means of diagnosing PC. Focal CK19 staining may be found in benign lesions, but diffuse positivity is characteristic of PC. HBME-1 positivity indicates malignancy but not papillary differentiation. Only rarely are all three markers negative in PC; this panel therefore provides an objective and reproducible tool for the analysis of difficult thyroid nodules.

Adenocarcinoma, Follicular↗
PubMed2001

The influence of patients' concerns on surgeons' recommendations for early breast cancer.

This paper examines whether an older patient's concerns about surgical treatment of breast cancer--such as fear of dying or about losing a breast--affect the treatment recommendations by their surgeons. A sample of 137 older women diagnosed with early stage breast cancer between 1994 and 1996 were interviewed within 2 months of diagnosis to determine demographic characteristics, their attitudes about breast cancer treatments, and which surgical treatment their surgeon initially recommended. The treatment preferences of the 35 surgeons treating these women were ascertained by asking them what treatment they would usually recommend to a hypothetical 75-year-old woman with early stage breast cancer. Patients who reported their feelings about losing a breast as 'very important' were less likely to be recommended mastectomy (Odds Ratio (OR) = 0.39; 95% (Confidence Interval) CI 0.16, 0.94), while patients who reported fear of dying from breast cancer as 'very important' were more likely to be recommended mastectomy (OR = 4.60; 95% CI 1.94, 11.59), after adjusting for surgeons' age and the surgeons' treatment preference when presented with a hypothetical patient. It is concluded that surgeons integrate patients' attitudes and concerns into their treatment recommendations.

Aged↗
PubMed2001

Postmenopausal hormone replacement therapy use by older Mexican-American women.

OBJECTIVES: To determine the prevalence of current hormone replacement therapy (HRT) use and describe its correlates among community-dwelling, Mexican-American women aged 67 and older. DESIGN: A population-based survey of older Mexican-Americans conducted in 1995/1996. SETTING: Five Southwestern states: Texas, New Mexico, California, Arizona, and Colorado. PARTICIPANTS: An area probability sample of 1,424 noninstitutionalized Mexican-American women aged 67 and older (mean age = 75.1) completed the survey instrument via a 90-minute in-home interview, which included examination and recording of all medications taken. MEASUREMENTS: Current use of HRT. RESULTS: In this sample of older Mexican-American women, 4.7% were current users of HRT. Controlling for sociodemographic characteristics (age, marital status, living arrangements, years of education, income, language of interview), current HRT use is significantly related to years of education (per each year) (odds ratio (OR) = 1.13; 95% confidence interval (CI) = 1.05-1.20), having had a hysterectomy (OR = 4.37; 95% CI 2.50-7.64), a diagnosis of osteoporosis (OR = 3.40, 95% CI = 1.58-7.33), age at menopause (per each year) (OR = 1.07; 95% CI = 1.03-1.12), ever having a mammogram (OR = 3.72; 95% CI = 1.66-8.37), ever having a Pap test/pelvic examination (OR = 2.11; 95% CI = 1.08-4.12), having spoken with a pharmacist within the past year regarding health conditions (OR = 1.96; 95% CI = 1.06-3.65), and having Medicare plus private insurance (OR = 2.13; 95% CI = 1.14-3.97). CONCLUSION: The prevalence of HRT use is lower than that reported in the older non-Hispanic white female population. In general, these findings indicate that access to and utilization of the traditional U.S. health care system are indicators of HRT use.

Activities of Daily Living↗
PubMed2001

Lymphoid cell infiltration into Epstein-Barr virus-positive nasopharyngeal carcinomas.

OBJECTIVES: A pilot study was designed to analyze lymphoid cell infiltration in Epstein-Barr virus-positive (EBV+) nasopharyngeal carcinomas (NPCs) and to determine whether this pattern of infiltration is consistent with non-EBV+ head and neck carcinomas or with solid EBV+ tumors in other locations. STUDY DESIGN: We performed a retrospective analysis of archived NPCs and oral cavity carcinomas. METHODS: Immunohistochemical staining of the archive material for various markers (CD3, CD8, UCHL-1, S-100, and intercellular adhesion molecule) was performed. Polymerase chain reaction techniques to establish the presence of the EBV genome were used. Cells in different locations were counted under a light microscope by 2 of the authors. RESULTS: The infiltration pattern of NPCs was different from that of oral cavity carcinomas. Stromal infiltration was significantly denser in oral cavity carcinomas. Tumor nest infiltration was more pronounced in NPCs. The pattern of infiltration was comparable with what has been described for other solid EBV+ tumors. CONCLUSIONS: The immune response to NPCs is likely to be strongly influenced by the presence of the EBV genome. The pattern of infiltration is similar to that of other non-head and neck EBV+ solid tumors and different from that of EBV- head and neck carcinomas.

Antigens, CD↗
PubMed2001

Cause of death in patients with well-differentiated thyroid carcinoma.

OBJECTIVES: The aim of this study is to examine in detail patients dying of well-differentiated thyroid carcinoma. STUDY DESIGN: A retrospective chart review with follow-up. METHODS: Data were collected from 522 consecutive cases of differentiated thyroid carcinoma treated by one endocrinologist and four surgeons at Mount Sinai Hospital, Toronto, Ontario, Canada, from 1964 to 1999. RESULTS: Ten patients died as a direct result of thyroid carcinoma; 19 other deaths were unrelated. Five of 102 patients were men (5%) and 5 of 420 were women (1%); the median age at diagnosis was 68.5 years (range, 49-82 y). No cases were stage I; three, stage II; two, stage III; and five, stage IV. Pathologically papillary carcinoma was found in six of the patients who died, follicular carcinoma in three patients, and Hurtle cell carcinoma in one patient. The causes of death were local invasion or compression of the trachea in two cases and distant metastases in eight patients. Median survival was 3.5 years (range, 1 mo-20 y). CONCLUSIONS: All patients dying of well-differentiated thyroid carcinoma had neck nodes, extrathyroidal spread, or distant metastases at presentation and were older than 49 years of age. Many presented because of their distant metastases. Death resulting from local disease was unusual, with most patients dying of distant metastases.

Adenocarcinoma↗
PubMed2001

Trends in sun protection behaviour among Australian young adults.

OBJECTIVE: To study changes in sun protection behaviour, exposure and sunburn that occur from late adolescence to young adulthood. METHOD: A longitudinal design was used to survey a cohort on their sun-protection behaviour from the middle of their final year at school to more than three years after finishing school. RESULTS: Males reported higher exposure, less use of sunscreen and deeper tans than females. Yet males wore hats more frequently. People with skin that just burnt were more likely to protect themselves from the sun than people with skin that tanned. Longitudinally, the level of reported exposure and the depth of tan declined, frequency of covering up, hat wearing and sunscreen use remained unchanged, and a slight U-shaped trend was observed for sunburn. CONCLUSIONS: Young adulthood may be an important time where deteriorating trends for sun protection found in the teen years are averted. Males are at greater risk of sun exposure than females. IMPLICATIONS: It is recommended that health promotion programs capitalise on the trend of improved sun-protective behaviours during the transition from adolescence to young adulthood, with a particular focus on young men.

Adult↗
PubMed2001

Isolation of antibody to human placental alkaline phosphatase (PLAP) from extracts of human placentae.

PROBLEM: Human placental alkaline phosphatase (PLAP) is a unique placental antigen bound to the syncytiotrophoblast, which may be able to elicit a specific immune response in pregnancy. METHOD OF STUDY: Antibody to PLAP was purified from placental extracts by: a) acid elution of membrane vesicles; b) purifying complexes of PLAP with human antibody on monoclonal antibodies to PLAP followed by denaturation of the enzyme; and c) by denaturation of PLAP in placental extracts and purification of antibody to PLAP on PLAP columns. RESULTS AND CONCLUSIONS: Specific antibody to PLAP is present in placental extracts, and is mostly bound to placental membrane preparations. PLAP is therefore immunogenic in pregnancy and could serve as a useful monitor of pregnancy-specific immunological responses. Since a similar enzyme appears in some cancers, it is possible that the immunization against PLAP in pregnancy will help to protect against the development of ovarian and endometrial cancer (the 'fetal antigen' hypothesis).

Alkaline Phosphatase↗
PubMed2001

HIV transmissions from a window-period platelet donation.

Recently, blood centers began investigational testing for HIV RNA by pooled nucleic acid testing (NAT). A 35-year-old frequent platelet donor tested HIV p24 antigen positive, antibody negative before implementation of NAT. He made 2 platelet donations (day -4 and -11) immediately before testing positive for HIV. The donor's HIV seroconversion was monitored, and stored samples were tested retrospectively for HIV RNA. Platelet recipients were tested for HIV infection. The day -4 sample tested positive for HIV RNA by pooled and individual sample NAT. The day -11 sample tested negative for HIV RNA by both NAT tests. The 2 recipients of the day -4 platelets tested HIV RNA and p24 antigen positive. The recipient of the day -11 platelets could not be tested because he had died. HIV NAT would have prevented transmission of HIV had it been available at the time of this donor's HIV seroconversion.

Adult↗
PubMed2001

Brush biopsy for detection of nasopharyngeal cancer.

The technique described above for sampling the nasopharynx requires minimal equipment, instruction, and expertise and causes minimal morbidity. Hence, it may be a valuable tool in a widespread screening program for a far too common and debilitating cancer in certain parts of the world.

Biopsy↗
PubMed2001

Older Mexican-American women and cancer screening: progress toward targets for healthy people 2000.

BACKGROUND: Published information about cancer screening in older Mexican-American women is scarce. This study reported the patterns of mammogram and Pap test use among older Mexican-American women. The patterns and associated factors were examined and compared with Healthy People 2000 targets. METHODS: Data were obtained from the Hispanic Established Population for the Epidemiological Study of the Elderly, the largest representative survey of community-dwelling Mexican Americans aged 67 years or over, from the southwestern United States. RESULTS: Among older Mexican-American women, 68.3% reported ever having a mammogram, and 41.2% reported having a mammogram in the last two years; 64.0% reported ever having a Pap test, with 43.6% reported having a Pap test in the last three years. CONCLUSIONS: The data for older Mexican-American women demonstrated that they approached the targets for breast cancer screening, but not for Pap test use.

Aged↗
PubMed2000

alpha-Actinin is a potent regulator of G protein-coupled receptor kinase activity and substrate specificity in vitro.

G protein-coupled receptor kinases (GRKs) phosphorylate G protein-coupled receptors, thereby terminating receptor signaling. Herein we report that alpha-actinin potently inhibits all GRK family members. In addition, calcium-bound calmodulin and phosphatidylinositol 4,5-bisphosphate (PIP2), two regulators of GRK activity, coordinate with alpha-actinin to modulate substrate specificity of the GRKs. In the presence of calmodulin and alpha-actinin, GRK5 phosphorylates soluble, but not membrane-incorporated substrates. In contrast, in the presence of PIP2 and alpha-actinin, GRK5 phosphorylates membrane-incorporated, but not soluble substrates. Thus, modulation of alpha-actinin-mediated inhibition of GRKs by PIP2 and calmodulin has profound effects on both GRK activity and substrate specificity.

Actinin↗