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Biomedical subjects

K Harper

Publications and source records attributed to K Harper.

At least 37 records · Page 2Linked to original sources
PubMed1996

Co-amplification to tail-to-tail copies of MuRVY and IAPE retroviral genomes on the Mus musculus Y chromosome.

We have isolated a clone from a C57BL/6 genomic library that contains both part of the Y Chromosome-specific 8.7 kbp MuRVY genome (Hutchinson and Eicher, J. Virol. 63, 4043, 1989) and a full-length 8.3 kbp Intracisternal A Particle genome (IAPE-Y), in a tail-to-tail organization. Although IAPs are encoded by a disperse multigene family (approximately 1000 copies per haploid genome), we present evidence that a significant proportion of the IAP-related sequences are present on the Y Chromosome (Chr) and that a >25 kbp genomic sequence, which contains the two proviral genomes, has been amplified on the Y Chr. Two discrete amplified families of MuRVY retroviral genomes distinguishable by a polymorphic restriction site were detected, suggestive that amplification occurred in incremental stages. The presence of MuRVY-related DNA sequences, but absence of IAPE-Y-related DNA sequences in Mus spretus suggests that the IAPE-Y retrotransposition event occurred after the evolutionary divergence of the lineages leading to Mus musculus and Mus spretus, and that the amplification of MuRVY occurred independently in the two lineages.

Animals↗
PubMed1995

Comparison of proximal isovelocity surface area method with pressure half-time and planimetry in evaluation of mitral stenosis.

OBJECTIVES: This study sought to 1) compare the accuracy of the proximal isovelocity surface area (PISA) and Doppler pressure half-time methods and planimetry for echocardiographic estimation of mitral valve area; 2) evaluate the effect of atrial fibrillation on the accuracy of the PISA method; and 3) assess factors used to correct PISA area estimates for leaflet angulation. BACKGROUND: Despite recognized limitations of traditional echocardiographic methods for estimating mitral valve area, there has been no systematic comparison with the PISA method in a single cohort. METHODS: Area estimates were obtained in patients with mitral stenosis by the Gorlin hydraulic formula, PISA and pressure half-time method in 48 patients and by planimetry in 36. Two different factors were used to correct PISA estimates for leaflet angle (theta): 1) plane-angle factor (theta/180 [theta in degrees]); and 2) solid-angle factor [1-cos(theta/2)]. RESULTS: After exclusion of patients with significant mitral regurgitation, the correlation between Gorlin and PISA areas (0.88) was significantly greater (p < 0.04) than that between Gorlin and pressure half-time (0.78) or Gorlin and planimetry (0.72). The correlation between Gorlin and PISA area estimates was lower in atrial fibrillation than sinus rhythm (0.69 vs. 0.93), but the standard error of the estimate was only slightly greater (0.24 vs. 0.19 cm2). The average ratio of the solid- to the plane-angle correction factors was approximately equal to previously reported values of the orifice contraction coefficient for tapering stenosis. CONCLUSIONS: 1) The accuracy of PISA area estimates in mitral stenosis is at least comparable to those of planimetry and pressure half-time. 2) Reasonable accuracy of the PISA method is possible in irregular rhythms. 3) A simple leaflet angle correction factor, theta/180 (theta in degrees), yields the physical orifice area because it overestimates the vena contracta area by a factor approximately equal to the contraction coefficient for a tapering stenosis.

Adult↗
PubMed1995

Group supervision of group psychotherapy.

OBJECTIVE: To explore the practice of group supervision of group psychotherapists using a process model. METHOD: The need for supervision and the advantages of the supervisory group setting are discussed highlighting the varying levels of interaction between the therapeutic system and the supervisory system. Assumptions basic to successful supervision are discussed. CONCLUSION: The processes leading therapists to understand that their experience in the supervision system can be an unconscious retelling of their clients' experience in the therapy group are explored.

Humans↗
PubMed1994

Glomerular mesangial cells in vitro synthesize an aggregating proteoglycan immunologically related to versican.

Recent studies have shown that mesangial cells derived from human adult glomeruli synthesize a number of 35S-labelled proteoglycans including a large chondroitin sulphate proteoglycan (CSPG), two dermatan sulphate proteoglycans (biglycan and decorin) and two heparan sulphate proteoglycans [Thomas, Mason and Davies (1991) Biochem. J. 277, 81-88]. In the present study we have examined the interaction of these proteoglycans with hyaluronan (HA) using associative gel chromatography. Only the large CSPG bound to HA, with 60% of those molecules in the medium and 80% of those in the cell layer being able to interact. Reduction and alkylation, or treatment of the monomer CSPG with proteinases, prevented the formation of aggregates, suggesting that the core protein was involved. The aggregates formed between purified CSPG and HA could be dissociated in the presence of HA-oligosaccharides of at least 10 monosaccharides in length. The inclusion of link protein with CSPG and HA promoted the formation of aggregates. Experiments with 3H-labelled mesangial-cell proteoglycans confirmed that only the large CSPG, with core protein molecular masses of 400 kDa and 500 kDa, interacted with HA. After chondroitin ABC lyase treatment of CSPG isolated from conditioned culture medium, several bands similar to those observed with 3H-labelled core proteins were identified using a polyclonal antiserum that recognizes versican. A monoclonal antibody recognizing the 1-C-6 epitope in the G1 and G2 globular regions of aggrecan did not recognize either mesangial-cell CSPG or bovine aortic versican. Northern-blot analysis confirmed that human mesangial cells express versican. Thus human mesangial large CSPG is a member of the versican family of proteoglycans. The interaction of CSPG and HA within the glomerulus may be important in glomerular cell migration and proliferation.

Adult↗
PubMed1994

Paraplegia in a patient with Marfan's syndrome as a result of a thoraco-abdominal aortic aneurysm repair.

Marfan's syndrome is a hereditary disorder involving a deficit in connective tissue collagen. Physical findings include musculoskeletal, ocular, and cardiovascular abnormalities. A 29-year-old man with a history of Marfan's syndrome was admitted to the hospital with back and chest pain secondary to a dissecting aortic aneurysm. He later underwent surgical aortic bypass graft surgery. Postoperatively, he was paraplegic. Our impression was anterior spinal artery syndrome due to prolonged cross-clamping of the aorta during surgical repair. This paper shows the risk of paralysis resulting from surgical repair of an aortic aneurysm as a poorly documented complication of Marfan's syndrome.

Adult↗
PubMed1994

Examination findings in legally confirmed child sexual abuse: it's normal to be normal.

BACKGROUND: Studies of alleged victims of child sexual abuse vary greatly in the reported frequency of physical findings based on differences in definition of abuse and of "findings." This study was designed to determine the frequency of abnormal findings in a population of children with legal confirmation of sexual abuse, using a standardized classification system for colposcopic photographic findings. METHODS: Case files and colposcopic photographs of 236 children with perpetrator conviction for sexual abuse, were reviewed. The photos were reviewed blindly by a team member other than the examiner, and specific anatomical findings were noted and classified as normal to abnormal on a scale of 1 to 5. Historical and behavioral information, as well as legal outcome was recorded, and all data entered into a dBase III program. Correlations were sought between abnormal findings and other variables. RESULTS: The mean age of the patients was 9.0 years (range 8 months to 17 years, 11 months), with 63% reporting penile-genital contact. Genital examination findings in girls were normal in 28%, nonspecific in 49%, suspicious in 9%, and abnormal in 14% of cases. Abnormal anal findings were found in only 1% of patients. Using discriminant analysis, the two factors which significantly correlated with the presence of abnormal genital findings in girls were the time since the last incident, and a history of blood being reported at the time of the molest. CONCLUSIONS: Abnormal genital findings are not common in sexually abused girls, based on a standardized classification system. More emphasis should be placed on documenting the child's description of the molestation, and educating prosecutors that, for children alleging abuse: "It's normal to be normal."

Child↗
PubMed1992

Hageman factor deficiency presentation and implications for management.

One of the more fascinating aspects of patient management arises when dealing with coagulation disorders. Factor XII deficiency, first described by Ratnoff in 1968, is one such coagulation disorder which provides some interesting challenges in management. Factor XII deficiency has been shown to be an inherited autosomal recessive disorder. The presence of Hageman factor abnormality trait can be clinically suspected in a patient with a prolonged activated partial thromboplastin time (APTT), normal prothrombin time (PT), normal bleeding time, and no clinical history of bleeding. Once suspected, the deficiency can be confirmed by normalization of partial thromboplastin time (PTT) with normal aged plasma and by factor assay. The importance of understanding the mechanism of factor XII deficiency has clinical significance when attempts are made to heparinize individuals who have this deficiency. Three methods can be used to monitor therapy: the chromogenic heparin assay, the citrated thrombin time, and the recalcified thrombin time. Two cases are presented.

Aged↗
PubMed1991

Differential regulation of HLA-A3 and HLA-B7 MHC class I genes by IFN is due to two nucleotide differences in their IFN response sequences.

The transcription of HLA-A3 and HLA-B7 class I genes is differentially regulated by IFN-alpha and -gamma, the latter gene being more inducible than the former. To determine the structural basis of this differential response, hybrid genes were constructed in which complete or fragmented HLA-A3 or HLA-B7 promoters were fused to the chloramphenicol acetyl transferase coding sequence. These constructs were tested in transient transfection assays, and the differential response of the HLA-A3 and HLA-B7 genes to IFN was correlated with nucleotide differences in their interferon response sequences (IRS). Replacement of two T nucleotides in the HLA-A3 IRS by the homologous A and C nucleotides of the HLA-B7 IRS was sufficient to impart IFN inducibility of the HLA-A3 promoter and efficient binding of constitutive and IFN-induced nuclear factors to the IRS of HLA-A3. Since the same two nucleotide differences are shared by all sequenced HLA-A and HLA-B genes, these results suggest that high or low responsiveness to IFN might be a locus-related property.

Base Sequence↗
PubMed1991

CTLA-4 and CD28 activated lymphocyte molecules are closely related in both mouse and human as to sequence, message expression, gene structure, and chromosomal location.

CD28, initially detected on human T lymphocytes with the help of antibodies, and CTLA-4, obtained by reverse genetics through its preferential expression in mouse activated T cells, are both single-V domain members of the Ig superfamily. Early work showed a relationship between these two molecules, which we wished to further document, in particular because of the growing realization of the functional importance of CD28 in some T cell activation pathways. Isolation and analysis of the mouse CTLA-4 gene and further analysis of the human CTLA-4 gene showed that both of these and the human CD28 gene share the same overall intron/exon organization. The nucleic acid sequence homology of the exons was found to extend across both molecules and species, whereas the 5' and 3' flanking regions exhibited homology across species but not between molecules. Message expression of human CTLA-4 was only detected in activated T cells and, thus, shares with that of mouse CTLA-4 and of mouse and human CD28 a lymphoid tissue distribution, although apparently broader for the latter. Two main human CTLA-4 transcripts of about 1.8 and 0.8 kb were detected, the smaller of which may derive, as reported for human CD28, from the use of an alternate degenerated polyadenylation signal sequence. The nucleic acid sequence data allowed a direct comparison of the four putative complete protein sequences of CD28 and CTLA-4 in the mouse and the human, showing striking homologies, especially in some stretches (such as a MYPPPY hexamer in the hinge region) conserved across molecules and across species. The mouse CD28 gene was localized to chromosome 1 band C by in situ hybridization with three different radioactive probes, indicating, together with previous data, that the CD28 and CTLA-4 genes map to the same chromosomal region in both the mouse and the human. Thus, CD28 and CTLA-4 were found to be strikingly similar in most respects, in terms of structure, sequence, expression, and gene location, furthermore in two species, strongly suggesting that their genes are the direct products of a duplication event and raising the possibility of functional homologies between the corresponding proteins.

Abatacept↗
PubMed1991

Differential transcription inducibility by interferon of the HLA-A3 and HLA-B7 class-I genes.

HLA-A3 and HLA-B7 class-I genes are differentially regulated in human T lymphoma Jurkat cells, at the transcriptional level, the expression of the HLA-B7 gene being selectively increased following alpha, beta or gamma interferon (IFN) treatment. Using a series of hybrid CAT constructs, associating HLA-A3 and HLA-B7 complete or fragmented promoters, the differential regulation was shown to be associated with 2 nucleotide differences at positions -176 and -175 in the interferon regulatory sequence (IRS) of the HLA-A3 and the HLA-B7 genes. Replacement, using site-directed mutagenesis, of the 2 thymidine in the HLA-A3-IRS by adenine and cytidine found at the same positions in the HLA-B7-IRS was sufficient to restore IFN inducibility of the HLA-A3 promoter and efficient interaction with HeLa nuclear factors. Since the same nucleotide differences are shared by all sequenced HLA-A and HLA-B class-I genes, the differential induction by IFN of the transcription of the HLA-A3 and B7 genes might be a general locus-related property.

Animals↗
PubMed1991

Admission dilemma.

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Decision Making↗
PubMed1990

Stiffness of the distal tip of bipolar pacing leads.

The stiffness of a bipolar pacing lead, particularly between anode and cathode, may be responsible for myocardial penetration and perforation. Following an unprecedented 7% incidence of high threshold exit block with a single model bipolar ventricular endocardial lead, a study was undertaken to compare pacing lead stiffness between anode and cathode of six models of bipolar leads from two manufacturers; Telectronics (T) and Medtronics (M). Four leads had polyurethane insulation; T 030-284 (Laser Dish), T 329-259 (Cordis, Encor), M 4012 (Target Tip), and M 4004 (Capsure). Two leads had silicone rubber insulation; M 5026 (Capsure) and M 5024 (Capsure SP). All leads were subjected to two stiffness tests. The Tip Deflection Test involved securing the lead at 45 degrees at the indifferent electrode and applying a force to deflect the tip 5 mm. The three point bending test involved placing the lead over two fixed bars in contact with the anode and cathode. Midway a third bar was pushed onto the lead and the force to deflect the lead 2 mm was recorded. The results showed that pacing leads with polyurethane insulation were much stiffer than those with silicone rubber insulation. The T 030-284 because of its construction was found to be the stiffnest. The next stiffnest was the M 4012. Both these leads had an unacceptable incidence of high threshold exit block; 7% with the T 030-284 (89 implants) and 3% with the M 4012 (102 implants). No cases of high threshold exit block were documented with the other four pacing leads and in particular the silicone rubber M 5026 (344 implants).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial↗
PubMed1990

Application of intragenic DNA probes in prenatal screening for retinoblastoma gene carriers in the United Kingdom.

Restriction fragment length polymorphisms (RFLPs) in 55 families affected by retinoblastoma have been studied using recombinant DNA probes derived from within the retinoblastoma predisposition gene. Only six families were uninformative for any of the DNA polymorphisms. The remaining 49 families can be offered prenatal screening. No obligate recombinations between any of the polymorphic loci and the retinoblastoma phenotype were observed. Four previously unknown cases of non-penetrance were identified. Prenatal testing for the inheritance of mutant alleles was performed in two cases and perinatal screening in two additional cases. One fetus inherited the normal allele from the affected parent and is therefore not at risk of retinoblastoma; the second fetus inherited the mutant allele and will require frequent screening for early detection of retinoblastoma. Both perinatal tests showed the absence of the mutant allele.

DNA Probes↗
PubMed1989

Inducible (class 3) aldehyde dehydrogenase from rat hepatocellular carcinoma and 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated liver: distant relationship to the class 1 and 2 enzymes from mammalian liver cytosol/mitochondria.

Peptides from rat liver aldehyde dehydrogenase (AIDH) induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment match the AIDH structure from HTC rat hepatoma cells (HTC-AIDH) at all positions examined, indicating induction of the same gene product by two independent routes. This 452 amino acid residue, class 3 AIDH structure differs substantially from the 500-residue AIDH structures isolated from normal liver cytosol (class 1) and mitochondria (class 2). Despite a 29.8% identity in 429 overlapping amino acids vs the human class 1 enzyme (27.7% vs class 2), neither the N- nor C-termini coincide, and gaps are introduced to optimize the alignment. Two residues placed in the active site of human liver AIDH by chemical modification, Cys-302 and Glu-268, are conserved in class 3 AIDH as Cys-243 and Glu-209. Cys-243/302 is the only cysteine residue conserved in all known AIDH structures. Gly-245 and Gly-250 of class 1/2 AIDHs, fitting the patterns of glycine residues in coenzyme binding fold of other dehydrogenases, are also conserved. Otherwise, Cys-49, Cys-162, and Glu-487, to which functional importance has also been ascribed, are not retained in the class 3 structure. Overall, a high conservation of Gly, Pro, and Trp and similar patterns of predicted secondary structure indicate general conservation of tertiary structure, as noted with other distantly related proteins. Three exon boundaries from the human liver mitochondria AIDH gene directly correspond to the N-terminus of the rat class 3 protein and to two of the gaps in the alignment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Dehydrogenase↗
PubMed1989

Novel structures CTLA-2 alpha and CTLA-2 beta expressed in mouse activated T cells and mast cells and homologous to cysteine proteinase proregions.

Differential screening of a subtracted cDNA library led to the detection of two distinct but homologous mouse cDNA, called CTLA-2 alpha and CTLA-2 beta. The corresponding transcripts have a tissue distribution restricted to T lymphocytes, where they are inducible upon activation, and to mast cells. The open-frame regions of both cDNA encode proteins homologous to cysteine proteinase precursors, remarkably, however, only to the proregion of these. The ctla-2 alpha and ctla-2 beta genes both map to the C1 band of mouse chromosome 13. Sequence comparisons suggest that the proregion of an ancestor proteinase gene evolved to the ctla-2 genes by successive duplications, first to autonomy, then to amplification. These results raise the question of the possible role of cysteine proteinase proregions, of cysteine proteinases themselves and of inhibitors thereof in activated T lymphocytes; from a different point of view, they also show that some protease proregions may have evolved as autonomous modules.

Amino Acid Sequence↗