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Biomedical subjects

J Haley

Publications and source records attributed to J Haley.

At least 19 recordsLinked to original sources
PubMed2005

Rare cause of right heart failure: contained rupture of a sinus of Valsalva aneurysm associated intraventricular septal aneurysm.

Sinus of Valsalva aneurysm (SVA) is a rare congenital lesion described first in 1840 by John Thurnam (Cited by Boutefou JM, Moret PR, Hahn C, Hanf E. Aneurysms of the sinus of Valsalva: report of seven cases and review of the literature. Am J Med 1978;65:18-24). In most cases unruptured Sinus of Valsalva aneurysm (SVA) is clinically silent; however, if it progressively enlarges it may cause coronary artery compression, complete heart block, or right ventricular outflow tract obstruction (Meier JH, Seward JD, Miller FA, Oh J, Sarano ME. Aneurysms in the left ventricular outflow tract: clinical presentation, causes, and echocardiographic features. J Am Soc Echocardiogr 1998;11:729-45; D'Silva SA, Dalve BV, Lokhandwala YY, Kale PA, Tendolkar AG. Unruptured congenital aneurysm of the left sinus of Valsalva presenting as acute right heart failure. Chest 1992;101:578-79) or is a potential source of cerebrovascular emboli. (Shahrabani RM, Jairaj PS. Unruptured aneurysm of the sinus of Valsalva: a potential source of cerebrovascular embolism. Br Heart J 1993;69:266-67). In this report, we describe a case of right coronary sinus of Valsalva aneurysm with a contained rupture. The containing rupture is in intraventricular septal aneurysm; the patient presents with right-sided heart failure.

Aged↗
PubMed2002

Systematic analysis of sequences of anti-DNA antibodies--relevance to theories of origin and pathogenicity.

Sequence analysis of anti-DNA antibodies is important in determining the molecular features which distinguish potentially pathogenic antibodies from those which are less likely to be pathogenic. Previous analysis of murine anti-DNA antibody sequences suggested that particular murine immunoglobulin genes are used preferentially to encode such antibodies and that somatic mutations to arginine, asparagine and lysine may be important in the creation of DNA binding sites. In this paper, a systematic analysis of published human anti-DNA sequences shows no strong evidence for preferential usage of particular human V(H) or V(L) genes in anti-DNA antibodies. Somatic mutations in IgG and IgA antibodies are clustered in the complementarity determining regions (CDRs) due to the effect of antigen drive. This process contributes to an excess of arginine, asparagine and lysine residues in these CDRs, some of which are likely to play an important role in binding to DNA. Computer modeling and in-vitro expression experiments are likely to help define the roles played by these residues in antigen binding and pathogenicity more clearly.

Amino Acid Sequence↗
PubMed2002

Molecular expression systems for anti-DNA antibodies--1.

Molecular expression systems can be used to produce whole antibodies or antibody fragments. The properties of these expression products can be tested in assays of binding or pathogenicity. Expression systems can be used to produce large quantities of antibodies which are already well-characterized, to produce new antibodies by repertoire cloning, or to produce slight modifications in the sequences of antibodies by mutagenesis prior to expression. This paper reviews the ways in which these methods have been used to study the structure and function of human and murine anti-DNA antibodies. A consistent finding, from experiments using a range of different expression methods and antibodies, is that sequence motifs including arginine residues play a major role in binding to DNA. These motifs can be present on either the heavy or the light chain, but are particularly reported in V(H)CDR3.

Animals↗
PubMed2001

The importance of somatic mutations in the V(lambda) gene 2a2 in human monoclonal anti-DNA antibodies.

2a2 is the most commonly rearranged gene in the human V(lambda )locus. It has been postulated that certain immunoglobulin genes (including 2a2) are rearranged preferentially because their germline sequences encode structures capable of binding to a range of antigens. Somatic mutation could then increase the specificity and affinity of binding to a particular antigen. We studied the properties of five IgG molecules in which the same heavy chain was paired with different light chains derived from 2a2. The pattern of somatic mutations in 2a2 was shown to be crucial in conferring the ability to bind DNA, but two different patterns of mutation each conferred this ability.Computer-generated models of the three-dimensional structures of these antibodies illustrate the ability of 2a2 to form a DNA binding site in different ways. Somatic mutations at the periphery of the DNA binding site were particularly important. In two different light chains, mutations to arginine at different sites in the complementarity determining regions (CDRs) enhanced binding to DNA. In a third light chain, however, mutation to arginine at a different site blocked binding to DNA.

Amino Acid Sequence↗
PubMed2001

Long-term care hospitals under Medicare: facility-level characteristics.

Though accounting for only a small percentage of total Medicare spending, long-term care hospitals (LTCHs) (defined as having an average length of stay [LOS] of 25 days or more) have been growing, in number and in Medicare expenditures, at a rapid rate in recent years. Because they have not been widely studied, we conducted research to describe the characteristics of this increasingly important Medicare provider type. We found that most LTCHs specialize in the provision of respiratory care or rehabilitation. Information from this study can help inform the development of a Medicare prospective payment system for LTCHs.

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PubMed2000

Lymphocyte predominance Hodgkin's disease: the use of bcl-6 and CD57 in diagnosis and differential diagnosis.

Distinction of lymphocyte predominance Hodgkin's disease (LPHD) from other forms of lymphoma often requires immunohistochemistry (IHC). Most previously published recommended panels include markers to define the large neoplastic cells (for example, CD20, J chain, CD45) as well as the non-neoplastic background cells (CD21, CD45RO, CD57, TiA 1). In the present study we examine the practical use of a double IHC method designed to look simultaneously at two germinal center specific cell types: bcl6+ cells and [bc16+, CD57+] co-positive cells. All 10 nodular LPHD had bcl6+ large cells and numerous CD57+ small background cells, including [bcl6+CD57+] cells in rosettes. One case of LPHD with large cell transformation contained numerous bcl6+ large cells both singly (in areas of typical LPHD) and in sheets (in foci of large cell transformation), many CD57+ small cells but few [bcl6+CD57+] co-positive cells and no rosettes. In none of the five cases of florid progressive transformation of germinal centers were true rosettes seen, although all contained variable numbers of bcl6+ large cells and CD57+ cells. Lymphocyte-rich classic Hodgkin's disease LRCHD cases were notable for bcl6 reactivity in Reed-Sternberg cells in all cases, numerous background small bcl6+ lymphocytes, and rare CD57+ cells. Two phenotypic profiles were associated with the 10 cases of T cell-rich B cell large cell lymphoma (TCRBCL). In the first, group "A," six of six cases had bc16- large cells and few CD57+ small cells, and none had significant numbers of [bcl6+, CD57+] co-positive cells. In the second, group "B," four of four cases had bcl6+ large cells with numerous CD57+ and [bcl6+, CD57+] co-positive cells. These findings not only show that LPHD can be distinguished from its morphologic mimics through identification of specific germinal center cell types, but also identifies a second group of TCRBCL (group "B") whose phenotype suggests it might be an architectural variant of nodular LPHD.

B-Lymphocytes↗
PubMed1998

Simple cyst in the postmenopausal patient: detection and management.

The aims of our study were to determine the prevalence of simple ovarian cysts in asymptomatic postmenopausal patients and to investigate the natural history of these cysts by ultrasonographic follow-up examinations. Three thousand five hundred and eighty-five women participated in the volunteer pelvic cancer screening program. Entry criteria were as follows: postmenopausal, no clinical symptoms, and no previous gynecologic pathology. An anechoic, small cyst less than 5 cm in greatest diameter was classified as a simple ovarian cyst. A scoring system to determine malignant potential had been established previously. All simple cysts had a score of 2 or less and had a morphology typical of benign lesions. In the case of a positive finding, the patient would be seen at 3 to 6 month intervals. The decision for surgical intervention was made by a private gynecologist or patient or if an interval change was noted. One thousand seven hundred and sixty-nine postmenopausal women (49.34% of all patients from the screening program) participated in this study. One hundred and sixteen simple cysts were found, with a prevalence of 6.6% in our population. Among those patients, 27 (23.28%) simple cysts resolved spontaneously, 69 (59.48%) have persisted, and 20 (17.24%) have been lost to follow-up study. Eighteen women (26.09%) with persistent simple ovarian cyst underwent surgery. No malignant ovarian conditions were identified. In conclusion, simple ovarian cysts are more common in postmenopausal women than previously was thought. This condition is very unlikely to be malignant and can be followed conservatively.

Adult↗
PubMed1997

Administration of long-term tamoxifen therapy modifies the plasma lipoprotein-lipid concentration and lipid transfer protein I activity in postmenopausal women with breast cancer.

Tamoxifen remains one of the most effective agents in the treatment of breast cancer. However, the development of persistent side effects from chronic administration of tamoxifen remains a concern. The objective of this project was to investigate the effect of long-term tamoxifen therapy (2 years) on the plasma lipoprotein concentration and lipid transfer activity in postmenopausal women diagnosed with breast cancer. Two distinct populations of breast cancer patients were recruited for this study: postmenopausal women diagnosed with breast cancer that have never been on tamoxifen and postmenopausal women diagnosed with breast cancer that have been on tamoxifen (20 mg once daily) for 2 years (n = 18 each group). Blood was collected for total and lipoprotein cholesterol (C) and triglyceride (TG) analysis by established enzymatic assays prior to and 2 years following the initial tamoxifen dose. To determine the effect of tamoxifen administration on lipid transfer between lipoprotein fractions, lipid transfer protein (LTP I) activity was measured. A significant decrease in total and low-density lipoprotein (LDL) cholesterol levels and a moderate increase in high-density lipoprotein (HDL) triglyceride levels were observed in plasma samples from postmenopausal women with breast cancer who were administered tamoxifen for 2 years. No significant differences in total and lipoprotein C and TG plasma levels were observed in samples from women with breast cancer that never received tamoxifen. LTP I activity was significantly decreased in patients receiving tamoxifen compared to patients who never received tamoxifen. These specific tamoxifen-induced effects may be important for a number of reasons. Although the apparent decrease in total C and LDL-C levels are favorable for reducing the risk of cardiovascular disease, the elevated levels of HDL-TG have been related to the increased risk of ischemic heart disease. Furthermore, understanding how tamoxifen influences LTP I activity provides valuable insight into how the administration of tamoxifen modifies plasma lipoprotein-lipid levels.

Aged↗
PubMed1997

Randomised controlled trial of cardiotocography versus umbilical artery Doppler in the management of small for gestational age fetuses.

OBJECTIVE: To compare the impact on use of resources in the management of small for gestational age babies using Doppler ultrasound versus cardiotocography. DESIGN: A randomised controlled trial. SETTING: A large district general hospital delivering 5500 to 6000 infants each year, 30% to 35% of which are to women of Pakistani origin. POPULATION: One hundred and fifty women delivered of small for gestational age infants. MAIN OUTCOME MEASURES: Primary outcome measures were length of hospital inpatient stay and induction of labour rates. Secondary outcome measures included caesarean section rates and length of stay on neonatal unit. RESULTS: The use of Doppler reduced average hospital inpatient stay from 2.5 days to 1.1 days, compared with cardiotocography (P = 0.036). There was no effect on induction of labour rates or caesarean section rates. There was no significant difference in length of stay on the neonatal unit (P = 0.33). There was a reduction in monitoring frequency and fewer hospital antenatal clinic visits. CONCLUSION: The use of Doppler ultrasound to manage small for gestational age infants reduces the use of resources, compared with cardiotocography.

Cardiotocography↗
PubMed1996

A mechanism for intergenomic integration: abundance of ribulose bisphosphate carboxylase small-subunit protein influences the translation of the large-subunit mRNA.

Multimeric protein complexes in chloroplasts and mitochondria are generally composed of products of both nuclear and organelle genes of the cell. A central problem of eukaryotic cell biology is to identify and understand the molecular mechanisms for integrating the production and accumulation of the products of the two separate genomes. Ribulose bisphosphate carboxylase (Rubisco) is localized in the chloroplasts of photosynthetic eukaryotic cells and is composed of small subunits (SS) and large subunits (LS) coded for by nuclear rbcS and chloroplast rbcL genes, respectively. Transgenic tobacco plants containing antisense rbcS DNA have reduced levels of rbcS mRNA, normal levels of rbcL mRNA, and coordinately reduced LS and SS proteins. Our previous experiments indicated that the rate of translation of rbcL mRNA might be reduced in some antisense plants; direct evidence is presented here. After a short-term pulse there is less labeled LS protein in the transgenic plants than in wild-type plants, indicating that LS accumulation is controlled in the mutants at the translational and/or posttranslational levels. Consistent with a primary restriction at translation, fewer rbcL mRNAs are associated with polysomes of normal size and more are free or are associated with only a few ribosomes in the antisense plants. Effects of the rbcS antisense mutation on mRNA and protein accumulation, as well as on the distribution of mRNAs on polysomes, appear to be minimal for other chloroplast and nuclear photosynthetic genes. Our results suggest that SS protein abundance specifically contributes to the regulation of LS protein accumulation at the level of rbcL translation initiation.

Chloroplasts↗
PubMed1996

Poor predictive value of platelet count, mean platelet volume and serum urate in hypertension in pregnancy.

OBJECTIVE: To determine the usefulness of platelet count, mean platelet volume and serum uric acid levels in the prediction of pre-eclampsia in women with mild hypertension in pregnancy, and to see if it is appropriate to base the management of such patients on these tests. SUBJECTS: Three hundred and thirty-six women attending the antenatal day unit with a diagnosis of non-proteinuric hypertension in pregnancy (diastolic blood pressure > or = 90 mmHg on two separate recordings) from whom at least one blood sample was taken. MAIN OUTCOMES MEASURED: The development of proteinuria (1+ or greater on urine Albustix); the need for oral antihypertensive medication, the need for the 'pre-eclampsia regime' intra- or post-partum; the need for induction of labour because of hypertension. RESULTS: No test, at any cut-off level, was found to be of any use in predicting the outcomes studied. Nor was a weekly change in any of the tests found to be of any use. CONCLUSION: Basing the management of patients with mild non-proteinuric hypertension on the results of platelet count, mean platelet volume or urate level is unwise as none of these tests was able to predict outcome in such patients.

Female↗
PubMed1995

Autoregulation of cloned human protein kinase C beta and gamma gene promoters in U937 cells.

Protein kinase C (PKC) serine/threonine kinases transduce cellular signals initiated by phospholipase C activation and diacylglycerol production. Human gene sequences from the beta and gamma isoforms were cloned and sequenced, and transcriptional regulation was studied. The major PKC beta transcription initiation site was identified by primer extension and S1 nuclease protection. Additional transcription initiation sites were located within a CpG-rich region proximal to the ATG. The transcription initiation site of the PKC gamma gene was identified by primed cDNA synthesis. In transfection experiments, the PKC gamma promoter was expressed at high level in U937 and HL60 cells but not in COS-1 cells. A sequence motif (AnAGATTCanAGAGnCa), reiterated over at least 1 kb, was located approximately 1.5 kb 5' of the PKC gamma translation initiation codon. This repetitive motif is abundant in run-on RNA in the hematopoietic and epithelial cell lines tested. Analysis of promoter deletion constructs by transient transcription assays in U937, IM9, and COS-1 cells showed negative regulation of the PKC beta promoter by sequences located between -3,000 and -690. although no homology between PKC beta and PKC-gamma 5'-flanking sequences was observed, both PKC beta and PKC gamma promoters were potently induced by 12-phorbol 13-myristate in transfected U937 cells.

Amino Acid Sequence↗
PubMed1994

Prevalence in a volunteer population of pelvic cancer detected with transvaginal ultrasound and color flow Doppler.

Our objective was to find the prevalence of non-symptomatic endometrial and ovarian neoplasms in a volunteer population of women, aged 40 and over. We offered a free volunteer screening program to asymptomatic women for a study using transvaginal ultrasound and color flow Doppler for the detection of pelvic cancer. In the first 2 years, 2117 women were examined, 51.3% post-menopausal. An ovarian cyst was defined as having a maximum diameter of more than 2.4 cm. Color flow was used to identify blood vessels feeding pelvic organs and adnexal enlargements. An abnormal Doppler flow velocity for the ovary was defined as a resistance index of less than 0.41. Ovarian cysts of less than 5 cm with normal Doppler indices were followed up in 6 months to 1 year. An adnexal morphology score was created to quantify the usefulness of this parameter, particularly in postmenopausal women. Indications for surgery were pre-defined as a persistent ovarian cyst of more than 5 cm, a persistent suspicious Doppler and a total endometrial thickness of greater than 0.59 cm in postmenopausal women not taking hormones.A total of 202 women (9.5%) had ovarian cysts. Fourteen women were operated upon because of size criteria, one because of family history and three for persistent abnormal flow. By Doppler study, 15 cysts were predicted to be benign and histology was confirmatory. There were two false positives and one true positive, a stage Ib ovarian cancer. There were no false negatives, although a stage I endometrioid cancer of the ovary was detected 8 months after a negative scan. In those cases in which follow-up data were available, 56% of the cysts regressed in premenopausal women. In postmenopausal women, 28% regressed. Twenty of 1086 postmenopausal women had endometrial biopsies. Three had endometrial cancer, two stage I and one stage IIA. Five had atypical or adenomatous hyperplasia, and seven had benign polyps. So many women have small asymptomatic cysts of the ovary that a major reorientation of physicians' attitudes towards the ovary will have to be introduced to adapt to this new information. In this population, the prevalence of benign epithelial ovarian neoplasms was 7/1000, and of malignancy was 05/1000. In postmenopausal women, the prevalence rate for endometrial cancer was 5/1000, with 5/1000 hyperplasias and 7/1000 benign polyps. When endometrial and ovarian cancer screening are combined, the yield is comparable to that seen in breast and cervical cancer screening.

Journal Article↗
PubMed1994

Total marrow failure induced by pegylated stem-cell factor administered before 5-fluorouracil.

To examine the potential role of stem-cell factor (SCF) in cancer chemotherapy, we have administered it to mice either before or after 5-fluorouracil (5-FU). When polyethylene glycolated (PEG-ylated) SCF was administered to mice before 5-FU, it had a significant sensitizing effect on primitive bone marrow cells. Examination of the hematopoietic status of these mice showed that the damage caused by 5-FU to both bone marrow and spleen hematopoiesis was exaggerated when it was preceded by SCF. SCF given before each of two 5-FU treatments at 7-day intervals resulted in the death of all treated mice. The time of death and hematopoietic status of these animals are compatible with the onset of hypoplastic marrow failure leading to pancytopenia and death. SCF given after 5-FU had little impact either on the initial degree of hematopoietic damage or subsequent recovery. Gut populations were similarly sensitized to 5-FU by prior treatment with SCF, and the damage caused to intestinal populations was greater than that resulting from 5-FU alone. This indicates that the different tissues may be similarly sensitized by SCF. The sensitizing effect of SCF was reversed by concurrent administration of transforming growth factor (TGF)-beta 3, and survival of the majority of the mice was ensured. Examination of hematopoiesis in mice treated concurrently with SCF and TGF-beta 3 showed that the degree of marrow and spleen damage had reverted to that caused by 5-FU alone. In further experiments, 100% survival and normal hematopoiesis could be attained by transplantation of 1 million syngeneic bone marrow cells 24 hours after 5-FU treatment following SCF sensitization. These data indicate that PEG-ylated SCF can sensitize normally resistant hematopoietic and gut stem cells to the effects of 5-FU. This sensitization resulted in effective eradication of hematopoiesis in SCF-pretreated/5-FU-treated animals and their subsequent death from marrow failure. These findings imply that SCF pretreatment may represent a novel method of increasing the effectiveness of conventional chemotherapy, making marrow ablation more effective without drug dose escalation and perhaps sensitizing some tumor cells to the effects of therapy.

Animals↗