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Biomedical subjects

S Hardy

Publications and source records attributed to S Hardy.

At least 73 records · Page 4Linked to original sources

Bronchoscopic and roentgenographic correlates of a positive transbronchial needle aspiration in the staging of lung cancer.

A study was conducted to determine the bronchoscopic and chest roentgenographic findings associated with a positive TBNA. One hundred fifty-seven of 465 patients who were diagnosed for the first time as having carcinoma of the lung had a positive aspirate. Bronchoscopic findings associated with a positive TBNA of N2 nodes were carinal widening and endobronchial disease, especially of the right upper lobe. Mediastinal adenopathy noted on chest roentgenograms and subcarinal nodes on CAT scans were associated with a positive aspirate as well. In 34 of 465 patients, TBNA was the only means of establishing the diagnosis of pulmonary malignancy. A useful, simple and safe procedure, TBNA can be used to stage the mediastinum in patients with lung cancer and is most likely to be positive with endobronchial and nodal disease. It can also facilitate therapeutic decision-making in patients whose surgical candidacy is marginal.

Biopsy, Needle↗

Issues in measuring change in motor function in children with cerebral palsy: a special communication.

Assessing clinical change in motor function in children with cerebral palsy is a complex measurement task. Whereas a variety of methods have been developed to quantify specific aspects of gross motor behavior (eg, gait analysis, electrophysiological tests, energy-consumption techniques), systematic measurement of overall gross motor function is a more difficult problem. This special communication reviews the structural and performance characteristics required of a well-developed, valid, and responsive clinically based evaluative measure. We discuss several recent approaches used to assess responsiveness and critically examine clinical measures used in randomized controlled trials of physical therapy for children with cerebral palsy. It is argued that the creation and validation of responsive evaluative measures is essential if we are to assess accurately whether our treatments do more good than harm.

Cerebral Palsy↗

An adenovirus early region 4 gene product is required for induction of the infection-specific form of cellular E2F activity.

E2F is a cellular, sequence-specific DNA-binding factor that binds to pairs of sites that occur upstream of the E1A and E2 early mRNA cap sites. During adenovirus infection, there is induction of a form of E2F that binds cooperatively to the pair of sites in the E2 control region. Production of the infection-specific E2F activity is dependent on early region 4 (E4), as extracts of cells infected with a mutant that lacks E4 did not contain this activity. Instead, two new forms of E2F were seen with the E4 mutant. Infection with mutant viruses unable to make E1A gene products produced the wild-type infection-specific E2F activity after a delay. Mutations in the E1B-55 kD-, E1B-21 kD-, E2-72 kD-, and E3-coding regions had no effect on production of infection-specific E2F. Analysis of cell lines confirmed the results obtained with mutant viruses. Cells that expressed E1A but not E4 genes (e.g., 293 cells) did not contain infection-specific E2F. Cell lines that expressed the E4 gene contained the activity. These observations demonstrate that E4 participates in the infection-induced change in E2F-binding activity. The data are consistent with E1A playing an indirect role in the process by mediating the efficient expression of E4 gene products which, in turn, induce the alteration in E2F activity.

Adenoviridae Infections↗

The gross motor function measure: a means to evaluate the effects of physical therapy.

This paper reports the results of a study to validate a measure of gross motor function in detecting change in the motor function of disabled children. Physiotherapists used this instrument to assess 111 patients with cerebral palsy, 25 with head injury and 34 non-disabled preschool children on two occasions, the second after an interval of four to six months. Parents and therapists independently rated the children's function within two weeks of each assessment, and a sample of paired assessments was videotaped for 'blind' evaluation by therapists. Correlations between scores for change on this measure and the judgments of change by parents, therapists and 'blind' evaluators supported the hypothesis that the instrument would be responsive to both negative and positive changes.

Adolescent↗

E2F from adenovirus-infected cells binds cooperatively to DNA containing two properly oriented and spaced recognition sites.

E2F is a sequence-specific DNA-binding factor which binds to sites that occur in pairs upstream of the adenovirus E1A and E2 early transcriptional start sites. Substantial quantities of E2F activity were found in uninfected-cell extracts, and there was a modest increase in E2F activity during an adenovirus type 5 (Ad5) infection. In uninfected cells, E2F was found to exist in multiple forms that could be separated chromatographically. Extracts prepared at 24 h after Ad5 infection contained a new form of E2F. This infection-specific form may have been a modified version of one of the forms present in uninfected cells. The infection-specific E2F was shown to bind cooperatively to a pair of E2F sites found upstream of the Ad2 early region 2 mRNA cap site. This binding was sensitive to the spacing between the sites and their relative orientation. In contrast, E2F binding in uninfected-cell extracts was unaffected by changes in orientation and spacing, consistent with very low cooperativity or independent binding.

Adenovirus Early Proteins↗

Automated reading of the microcytotoxicity test.

From studies of 16,993 reactions in the microlymphocyte cytotoxicity test, we concluded that automatic fluorescent readings are comparable to those produced by visual readings with eosin dye exclusion. The r values (counting only strong reactions as positive) were as follows: 0.94 fluorescence machine versus visual fluorescence reading; 0.96 eosin visual reading, reader 1 versus reader 1; 0.97 eosin visual reading, reader 2 versus reader 2; 0.91 eosin visual reading, reader 1 versus reader 2; 0.98 fluorescence machine 1 versus machine 1; 0.98 fluorescence machine 2 versus machine 2; 0.96 fluorescence machine 1 versus machine 2; 0.92 fluorescence machine versus eosin visual reading; It was further shown that there was 93% concordance in assignment of HLA specificities between machine-assigned specificities and assigned by an experienced technologist. Most of the extra reactions obtained by fluorescence were in the crossreactive groups. Thus, the extra positive reactions obtained by the machine were likely to be the result of greater sensitivity than detection of random extraneous reactions.

Cytotoxicity Tests, Immunologic↗

Living-related donor kidney transplants.

1. Black kidney graft recipients do poorly when compared to Caucasians and Asians. This effect is significant for both Black 2-haplotype identical and 1-haplotype identical sibling transplants. Since 1984 graft survival in Caucasian siblings was 90% at 3 years for 2-haplotype matches and 80% at 3 years for 1-haplotype matches. 2. CsA has had a 10% effect in 1-haplotype sibling transplants comparing the results from 1984 through 1989 to 1978 through 1983. The CsA effect is about a 5% difference in HLA-identical transplants. 3. Diabetic patients transplanted after 1984 had a significantly poor graft survival which was ameliorated when treatment was equivalent to ESRD patients with glomerulonephritis and pyelonephritis use of CsA in more recent times. 4. The transfusion effect was significant in 2-haplotype and 1-haplotype transplants in the 1978 to 1983 period and is now not significant in any LRD transplant categories. 5. HLA panel-reactive antibody did not effect graft survival of LRD transplants. 6. CsA has a significant effect on 1-haplotype transplants but no effect on 2-haplotype transplants.

Blood Transfusion↗

Adenoviral control regions activated by E1A and the cAMP response element bind to the same factor.

Transcription of adenoviral early genes is activated by viral E1A gene products. Four of the five early genes contain sequence homologies to the cAMP-inducible element identified in cellular genes. Co-purification and competition assays demonstrated that the adenovirus and cAMP-inducible transcriptional control regions bind the same factor or factors. Since the binding sites map to regions necessary for transcription of the three adenoviral early genes whose control regions were analyzed, it is likely that the activities play a role in their transcription.

Adenovirus Early Proteins↗

cAMP acts in synergy with E1A protein to activate transcription of the adenovirus early genes E4 and E1A.

The transcriptional control regions of several E1A-inducible adenovirus early genes contain sequences similar to the cAMP response element of several cellular cAMP-inducible genes. The cAMP-responsive cell line S49 was infected with wild-type adenovirus and found to contain elevated levels of mRNAs encoded by all early genes tested (E4, E1A, and E1B), following treatment with dibutyryl cAMP. This effect was at the level of transcriptional activation. The effect of cAMP on E4 and E1A transcription was greater in cells infected with wild-type virus than in cells infected with virus that lacked functional E1A proteins. cAMP in combination with E1A generated a greater induction than the product of the increases achieved by each inducer alone. Therefore, cAMP acted in synergy with E1A to induce maximally transcription of the E4 and E1A genes. These data suggest that E1A or E1A-stimulated events can interact functionally with targets of cAMP signaling in the cell to induce transcription of the adenovirus early genes.

Adenoviridae↗

Knowledge of cystic fibrosis in patients and their parents.

A standardized questionnaire was used to assess knowledge about cystic fibrosis in 28 patients with cystic fibrosis (aged 10 to 21 years) and in the parents of 25 of these patients. Knowledge of disease pathophysiology and treatment was generally comprehensive and detailed; knowledge of the genetics was fair. However, there were conspicuous deficits in the awareness of reproductive risks and of male sterility. Significant predictors of patient knowledge were patient age, sex, and educational level and parental age. Predictors of parent knowledge were Shwachman score, socioeconomic status, and sex of responding parent. Patients rely heavily on parents for information about cystic fibrosis. More than one third of both patients and parents sought more information about the disease and its implications.

Adolescent↗

Studies on the export of the maltose-binding protein and the LamB protein.

Two proteins encoded in the malB locus, the maltose-binding protein and the LamB protein, are exported to the periplasm and outer membrane, respectively. Both proteins are synthesized on membrane-bound polysomes in precursor forms which contain signal sequences at their amino-termini. Proteolytic removal of the signal sequence from maltose-binding protein begins co-translationally but is nat initiated until the nascent chains have attained 80% of their final length. Approximately one-third of the molecules are processed co-translationally, the remainder being processed post-translationally. In contrast, the LamB precursor is processed almost entirely post-translationally. In neither case is it clear when the polypeptide chains are transferred through the cytoplasmic membrane. An interesting feature with as yet unknown significance is the non-uniform rate of elongation of maltose-binding protein. The export of maltose-binding protein and the lamB protein as well as that of other proteins, has been shown to require an energized membrane.

ATP-Binding Cassette Transporters↗