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Biomedical subjects

C Lane

Publications and source records attributed to C Lane.

At least 37 records · Page 2Linked to original sources
PubMed1998

The thyrotropin receptor in thyroid eye disease.

Thyroid eye disease (TED) has an autoimmune etiology, but the nature of the autoantigen that is the target of the initiating event remains unknown. A number of candidates have been proposed based on Western blotting, library screening, and deduction from sequence similarity. A strong favorite is the thyrotropin receptor (TSHR), which is the target of the thyroid stimulating antibodies (TSAB) of Graves' disease (GD). We have recently demonstrated TSHR transcripts in orbital adipose tissue from a patient with TED by Northern blot, transcripts in normal adipose tissue being at the limit of detection. We have shown that the transcripts are translated into protein by immunohistochemical analysis using two monoclonal antibodies to the TSHR generated by genetic immunization. TSHR immunoreactivity is associated with elongated cells with the appearance of a fibroblast, often adjacent to clusters of adipocytes, in orbital biopsies from patients with TED but not in strabismus or pseudotumor biopsies. In animal studies, we have transferred thyroiditis to naive BALBc and NOD mice, using T cells primed to the human TSHR, either using the receptor expressed as a bacterial fusion protein or by genetic immunization. The BALBc develop a Th2-type response to the receptor, but the NOD a Th1-type with thyrocyte destruction. Orbital pathology, edema, infiltration by mast cells and lymphocytes, and adipose accumulation was also induced in 68% of the BALBc but none of the NOD mice. Together these data indicate that the preadipocyte expresses the TSHR and that a Th2 autoimmune response to the receptor may be an initiating event in TED.

Animals↗
PubMed1998

Human papillomavirus type 11 recombinant L1 capsomeres induce virus-neutralizing antibodies.

The human papillomavirus type 11 (HPV-11) L1 major capsid protein can be trypsinized to generate recombinant capsomeres that retain HPV genotype-restricted capsid antigenicity (M. Li, T. P. Cripe, P. A. Estes, M. K. Lyon, R. C. Rose, and R. L. Garcea, J. Virol. 71:2988-2995, 1997). In the present study, HPV-11 virion-neutralizing monoclonal antibodies H11.F1 and H11.H3, previously characterized as recognizing two distinct HPV-11 capsid-neutralizing antigenic domains (S. W. Ludmerer, D. Benincasa, and G. E. Mark III, J. Virol. 70:4791-4794, 1996), were each found to be highly immunoreactive with trypsin-generated capsomeres in an enzyme-linked immunosorbent assay (ELISA). Capsomeres were used to generate high-titer polyclonal immune sera that demonstrated HPV genotype-restricted reactivity by ELISA. The capsomere antisera were then tested in an in vitro infectivity assay and found to neutralize HPV-11 virions. In this assay, HPV-11 capsomere polyclonal antisera exhibited neutralization titers (10(-5) to 10(-6)) comparable to those obtained with a virion-neutralizing antiserum raised previously against intact HPV-11 VLPs (R. C. Rose, R. C. Reichman, and W. Bonnez, J. Gen. Virol. 75:2075-2079, 1994). These results indicate that highly immunogenic, genotype-restricted HPV capsid-neutralizing antigenic domains are contained entirely within capsomeres. Thus, capsomeres may be viable vaccine candidates for the prevention of HPV disease.

Animals↗
PubMed1998

Ratio of bcl-xshort to bcl-xlong is different in good- and poor-prognosis subsets of acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous collection of leukemic disorders ranging from chemotherapy-sensitive subsets [inversion 16 and t(8;21)], which often can be cured with cytosine arabinoside alone, to the most resistant subsets, which can survive even supralethal levels of combination alkylator chemotherapy (cytogenetic subsets monosomy 5 and monosomy 7). MATERIALS AND METHODS: To analyze the expression of BCL-2 family genes, which are expressed in these subsets of AML, we used PCR sequence amplification reactions that are dependent on oligonucleotide primers representing the BH1 and BH2 homology domains to generate the unique regions between BH1 and BH2. These primers are conserved among all members of the BCL-2 gene family and are separated by a 150 nucleotide region sequence between the BH1 and BH2 domains. The PCR products unique to each BCL-2 family member were cloned directionally into sequencing vectors. The identity of the insert of each clone was determined by slotblots of the DNA amplified from individual colonies and by hybridization with radioactive probes specific to the bcl-2, bcl-x, or bax genes. RESULTS: We found that bcl-2 is the predominant member expressed in AML samples with a poor prognosis (-5, -7), whereas the transcripts of bcl-x are higher than those of bcl-2 in the AML samples with a good prognosis [inv16, t(8;21)]. No significant difference in bax expression was detected between AML subsets of good and bad prognosis. The ratio of bcl-xlong, which inhibits apoptosis, to bcl-xshort, which promotes apoptosis, was determined by amplification with a pair of primers specific to bcl-x followed by separation of the PCR product on agarose gels. Bcl-xlong and bcl-xshort appeared as bands of different molecular mass on a molecular weight gel and were visualized by ethidium bromide staining or Southern blot analysis with a bcl-x-specific probe. CONCLUSIONS: We found that the ratio of bcl-x long to bcl-x short was higher in the AML patients with a poor prognosis. These experiments showed that the levels of BCL-2 family members in the leukemia cells of good- and poor-prognosis subsets are different. In addition, novel members of the BCL-2 family were isolated from the cells of AML patients of either prognosis.

Acute Disease↗
PubMed1997

MRI of the anterior optic pathways following enucleation.

We examined five patients who had enucleation of one eye for inflammatory or neoplastic disease, using MRI at 1.5 Tesla. None had symptoms referable to the enucleated orbit. In addition, age- and-sex matched individuals were imaged as control subjects, and a further 15 subjects, referred for other than orbital disease, were reviewed. Measurements were made retrospectively of the dimensions of the optic chiasm to establish normal values. All five patients showed abnormalities on MRI following enucleation: abnormal signal within the optic nerve remnant on short tau inversion recovery (STIR) images, and atrophy of the nerve remnant and the chiasm. These findings were not apparent in the control or normal subjects. Such findings are to be expected following enucleation and should not be interpreted as indicating active pathology.

Aged↗
PubMed1997

Heart disease education and prevention program targeting immigrant Latinos: using focus group responses to develop effective interventions.

Although research has provided considerable knowledge concerning the positive effects of behavioral change on morbidity and mortality from heart disease and related risk factors, some segments of the population have not benefited equitably from this information. In April 1995, the National Heart, Lung, and Blood Institute (NHLBI) conducted seven focus groups to determine knowledge and attitudes about heart disease and associated risk factors, identify media usage and preferences, and assess publications usage and preferences among Spanish-speaking Latino immigrants residing in the Washington, D.C., metropolitan area. This information was gathered to assist in the development of key messages and strategies for the NHLBI Latino Community Cardiovascular Disease Prevention and Outreach Initiative, Salud para su Corazón--a heart disease prevention and education campaign. Findings from these focus groups indicate that Latinos may not benefit from heart disease prevention messages developed for the general population because of language and cultural differences. The researchers concluded that health education and disease prevention programs targeting the Latino community should develop educational materials and interventions that address language preferences and cultural values. Furthermore, to be effective, these programs should show people how to make positive behavioral changes based on their current circumstances, while remaining sensitive to the fact that Latino immigrants face major life adjustments and many are still greatly influenced by their country of origin.

Adolescent↗
PubMed1997

Thyrotropin receptor transcripts in human adipose tissue.

Thyroid associated ophthalmopathy (TAO) is generally considered to have an autoimmune pathogenesis but the target antigen has yet to be identified. It is most frequently associated with Graves' disease and there is some logic in assuming that the same antigen, the thyrotropin receptor (TSHR), is the common link. Previous studies, mostly PCR based, aimed at investigating TSHR transcripts in the orbit, have yielded conflicting results, although there is circumstantial evidence for their presence in orbital fat. In this study, we have examined adult human adipose and muscle tissues from various locations, initially by PCR and subsequently by northern blot. We obtained the expected 610bp product in normal intestinal and orbital fat but not skeletal muscle, following two rounds of PCR amplification but only when reverse transcription used a TSHR specific primer. In northern blots, despite loading all of the RNA obtained from total normal orbital fat contents, TSHR transcripts were at the limit of detection and similarly for large samples of intestinal fat. The exception was RNA obtained from TAO orbital fat, in which TSHR transcripts of 4.6 and 1.7kb were clearly visible, as in the thyroid. We conclude that normal adult adipose tissues contain low levels of TSHR transcripts. In TAO, TSHR transcripts are elevated probably due to an increased number of cells, in particular of preadipocytes in orbital adipose tissue.

Abdomen↗
PubMed1996

Community leg ulcer clinics: a comparative study in two health authorities.

OBJECTIVE: To compare the outcome and cost of care for leg ulcers in community leg ulcer clinics in Stockport District Health authority with Trafford District Health Authority as a control. DESIGN: Detailed cost and efficacy studies conducted prospectively over a three month period in both districts both before and one year after the introduction of five leg ulcer clinics in Stockport. SETTING: Two large district health authorities of broad socioeconomic mix and total population of 540,000. PATIENTS: All patients receiving treatment for an active leg ulcer, irrespective of the profession or location of their carer. MAIN OUTCOME MEASURES: The proportion of ulcerated limbs completely healed within three months and total cost of leg ulcer care. RESULTS: The introduction of community clinics in Stockport improved healing of leg ulcers from 66/252 (26%) in 1993 to 99/233 (42%) in 1994 (P < 0.001) compared with in Trafford, where 47/203 (23%) healed in 1993 and only 43/213 (20%) in 1994. This improved result in Stockport was achieved while the annual expenditure on care of leg ulcers was reduced from 409,991 pounds to only 253,371 pounds. In the same year the cost of leg ulcer care in Trafford increased from 556,039 pounds to 673,318 pounds. CONCLUSION: In the first year after the introduction of community clinics, before most patients in Stockport had access to these clinics, healing of leg ulcers was already improved whereas costs were reduced.

Community Health Centers↗
PubMed1996

Accumulation of the endogenous L-arginine analogue NG-monomethyl-L-arginine in human end-stage renal failure patients on regular haemodialysis.

We measured plasma levels of L-arginine, its analogue NG-monomethyl-L-arginine (L-NMMA), and related amino acids in normal subjects and uraemic patients (n = 31), before and after haemodialysis. Plasma levels of L-arginine were reduced to less than half of normal values in uraemic subjects compared with controls, and were not affected by haemodialysis. L-NMMA was not detectable in non-uraemic subjects, but markedly elevated in uraemic patients. In parallel, we used human red blood cells as a model to study the effect of L-NMMA upon the transport of L-arginine. L-NMMA trans-stimulated L-arginine transport significantly, confirming that L-arginine and L-NMMA share common transport pathways. Our results suggest altered L-arginine metabolism and the presence of an increased concentration of a NO synthase inhibitor in uraemia. We propose that alterations in plasma L-arginine levels and increased production of L-arginine analogues will alter NO synthesis and may help to explain some pathological changes seen in uraemia.

Adult↗
PubMed1996

Influence of fixation accuracy on threshold variability in patients with open angle glaucoma.

PURPOSE: To evaluate the contribution that fixation errors make to the overall variability of perimetric responses in patients with glaucoma. METHODS: Frequency of seeing curves were established, with and without fixation error correction, at two locations in each of 14 patients with glaucoma and good visual acuity. One location corresponded to a relatively normal region of the visual field, whereas the second corresponded to a region in which there was a sensitivity deficit. All patients had an acuity of better than 20/63 (except one whose acuity was 20/100). The locations of the first and fourth Purkinje images of a collimated infrared source were used to give a measure of eye position, during each stimulus presentation (accuracy 10 minutes of arc). RESULTS: Considerable variation was found in patient fixation accuracy. In the worst case, fixation was within 30 minutes of the target in only 7% of presentations whereas in the best, it was within this range in more than 60%. No relationship was found between accuracy of fixation and extent of loss. The gradient of the frequency of seeing curve was found to be shallow at regions of reduced sensitivity, a finding that supports the recognized relationship between variability and sensitivity deficit. A recalculation of the frequency of seeing curves, using only those responses in which the patient's fixation was within a specified range ( < 60 minutes of arc), did not show a meaningful reduction in variability at either location. CONCLUSIONS: It is concluded that fixation errors, though contributing to variability, are not the major cause of the increased variability seen at locations with reduced sensitivity.

Aged↗
PubMed1996

Developing a skin-care protocol in radiotherapy.

Radiotherapy can cause a number of dermatological reactions. Treatment for these reactions needs to be research-based and standardised. A clear protocol helps health-care professionals select the appropriate treatments.

Humans↗
PubMed1995

Development of a cervical cancer education program for native American women in North Carolina.

The North Carolina Native American Cervical Cancer Prevention Project is a five-year, NCI-funded public health education program. The project was developed to address the problem of excess mortality from cervical cancer among Native American women by increasing screening and follow-up of abnormal cervical smears. This paper describes the process of developing and implementing the intervention, an individualized health education program. Development of the intervention was guided by the health belief model, social learning theory, self efficacy theory, and PRECEDE, a planning model. Community analysis revealed that the target populations had limited awareness of cervical cancer as a specific type of cancer, and had an experientially-based pessimistic outlook regarding survival with cancer. Steps in developing the cervical-cancer prevention program included 1) development of objectives, 2) selection of strategies and development of cervical cancer education materials, 3) pretesting and revision, and 4) implementation, monitoring, and further revision. Native American lay health educators were recruited and trained to deliver the program. The experience of developing and implementing the individualized health education program suggests that the design of health education programs for Native Americans should begin with examination of basic assumptions regarding the nature of health and illness in the target population. The unique cultures and the diversity of Native American populations are critical factors in the development of health education programs for them.

Adolescent↗