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Biomedical subjects

C Gregory

Publications and source records attributed to C Gregory.

At least 19 recordsLinked to original sources
PubMed1995

Dependent care, caregiver burden, hardiness, and self-care agency of caregivers.

This is a partial replication of a descriptive correlation study that examined the relationship between dependent care, caregiver burden, health-related hardiness, and self-care agency of caregivers. Data from this replication were compared with those of the previously reported study. Data were collected from a home health agency and a radiation-oncology unit. A moderate significant negative correlation was found between objective burden and dependent care. Moderate significant positive correlations were found between self-care agency scores and the commitment/challenge and control subscales of health-related hardiness scores. The major difference between this study and the previous one was in the level of subjective burden. Even though caregivers reported greater levels of subjective burden, the correlation with self-care agency and hardiness was nonexistent. The small subsample of male caregivers (n = 14) prevented a statistical comparison with the previous data; however, in the pooled sample previous findings were supported.

Adaptation, Psychological↗
PubMed1994

User-definable bull's-eye database analysis.

Several quantitative bull's-eye database programs have been developed and employed successfully, but generally they restrict the user to limited types of quantitative analysis. We developed a type of bull's-eye analysis which facilitates user-defined processing, and then explored the effects of various types of processing on the comparisons of patient information with that of reference databases. Male and female bull's-eye database were generated from 32 normal patients using unweighted 2D prefiltering, ramp backprojection, unweighted 3D postfiltering, and peak value circumferential plotting (base method). The data from each patient were then reprocessed and compared to the databases by means of three different approaches: (1) using the base method, (2) using average as opposed to peak value profiles, and (3) using a resolution recovery prefilter instead of a smoothing prefilter. Significant differences in the number of apparently abnormal regions were found between the three methods. In other words, the type of single-photon emission tomography (SPET) processing affected the accuracy of comparisons between patient and database information. Because even sophisticated analysis can now be performed on personal computers, we conclude that, rather than a preprocessed data file, clinical "normal reference" information should consist of original SPET data (in a standard format, e.g., Interfile) from a series of documented normal patients. Each user could then generate reference bull's-eye database by applying his or her own clinical processing procedures to the data.

Humans↗
PubMed1994

Pharmacological management of schizophrenia in older patients.

Although antipsychotic drugs are the mainstay of treatment in older patients with schizophrenia, much of the theoretical work underpinning their use is based on evidence gained from younger patients. With respect to dosages, there has been little work comparing plasma concentrations of antipsychotics in older patients with those of younger patients. However, there are well documented changes in the pharmacokinetics of these drugs in the elderly, particularly in their hepatic metabolism and renal excretion. There is also evidence that older patients experience more adverse effects from antipsychotics than younger patients. Such effects include extrapyramidal symptoms, postural hypotension and falls. For these reasons it is recommended that starting doses of antipsychotic drugs in older patients should be in the region of 25 to 50% of that recommended for younger patients, and should be slowly increased. Selection of a particular antipsychotic agent is best made on the basis of individual patient characteristics and the adverse effect profiles of particular drugs.

Aged↗
PubMed1993

Rhodopsin mutations in autosomal dominant retinitis pigmentosa.

Retinitis pigmentosa is an inherited progressive disease which is a major cause of blindness in western communities. It can be inherited as an autosomal dominant, autosomal recessive, or X-linked recessive disorder. In the autosomal dominant form (adRP), which comprises about 25% of total cases, approximately 30% of families have mutations in the gene encoding the rod photoreceptor-specific protein rhodopsin. This is the transmembrane protein which, when photoexcited, initiates the visual transduction cascade. So far, 41 single-base-pair (bp) substitutions, one two-bp substitution, and four deletions ranging from 3 to 42 bp have been identified in this gene. These mutations do not appear to be significantly clustered in a specific part of the protein, but occur in all three major domains, namely the intradiscal, transmembrane, and cytoplasmic regions. Different mutations appear to cause differences in the severity of the disease, though there is considerable variability in severity even within the same family, at least in certain of these mutations. Identification of all the mutations involved in rhodopsin-RP should allow accurate and early detection of affected individuals, informed genetic counselling, as well as furthering our knowledge of the disease process involved.

Amino Acid Sequence↗
PubMed1993

A comparison of effect of temperature on phosphorus metabolites, pH and Mg2+ in human and ground squirrel red cells.

1. 31P NMR spectra were obtained at temperatures ranging from 2 to 30 degrees C from freshly drawn human (cold-sensitive) and ground squirrel (cold-tolerant) red cells. The concentration of ATP was also determined by luciferin-luciferase assay over the same temperature range. 2. The concentration of ATP as determined by NMR or by the luciferin-luciferase assay did not change with temperature in either species. The absolute concentration of ATP in human cells determined by NMR was not significantly different from the total ATP determined enzymatically. 3. The concentration of 2,3-diphosphoglycerate was higher and that of pyridine nucleotides lower in human than in ground squirrel red cells. This species difference was independent of temperature. 4. Intracellular pH, as determined from the positions of the NMR peaks of 2- and 3-phosphates of diphosphoglycerate, became more alkaline as the temperature was lowered. 5. Free intracellular magnesium, determined from the difference in the positions of the peaks for alpha- and beta-phosphorus of ATP, increased in the ground squirrel red cells and decreased in the human red cells with cooling from 30 to 2 degrees C. Total magnesium, as determined by atomic emission spectroscopy, did not change with temperature in red cells of either species. 6. The intensities of all phosphorus metabolite signals from the ground squirrel cells increased with decreasing temperature, while those from the human cells were unaffected. Since chemical shift anisotropy in the presence of magnesium is a powerful spin-lattice relaxation mechanism for phosphates, this is additional evidence for the temperature dependence of free magnesium concentration in the ground squirrel cells. 7. We conclude that there is no difference in phosphorus metabolites or intracellular pH which could account for the differential cold sensitivity in human and ground squirrel red cells. We suggest that, in the cold-tolerant red cells from the ground squirrel, magnesium is released from binding sites as the temperature is lowered. The change in free intracellular Mg2+ may account at least in part for the unusually low temperature sensitivity of the Na(+)-K+ pump in the red cells of this species.

2,3-Diphosphoglycerate↗
PubMed1991

Restricted Epstein-Barr virus protein expression in Burkitt lymphoma is due to a different Epstein-Barr nuclear antigen 1 transcriptional initiation site.

Epstein-Barr virus (EBV) expresses six nuclear antigens (EBNAs) and three integral latent membrane proteins (LMPs) in latently infected growth-transformed B lymphoblastoid cell lines (LCLs). In contrast, EBV protein expression in Burkitt lymphoma tissue or in newly established Burkitt lymphoma cell lines is frequently restricted to the EBV genome maintenance protein, EBNA-1. EBNA-1 expression in the absence of other EBNAs and LMP-1 has been an enigma since, in LCLs, all EBNA mRNAs are processed from a single transcript. We now show that the basis for restricted EBV expression in Burkitt lymphoma cells is selective EBNA-1 mRNA transcription from a hitherto unrecognized promoter that is 50 kb closer to the EBNA-1-encoding exon than previously described EBNA-1 promoters. Infected cells with EBNA-1-restricted expression could preferentially persist in vivo in the face of EBV-immune T-cell responses, which are frequently directed against other EBNAs and are also dependent on LMP-1 expression.

Amino Acid Sequence↗
PubMed1991

Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death.

Epstein-Barr virus (EBV) not only induces growth transformation in human B lymphocytes, but has more recently been shown to enhance B cell survival under suboptimal conditions where growth is inhibited; both effects are mediated through the coordinate action of eight virus-coded latent proteins. The effect upon cell survival is best recognized in EBV-positive Burkitt's lymphoma cell lines where activation of full virus latent gene expression protects the cells from programmed cell death (apoptosis). Here we show by DNA transfection into human B cells that protection from apoptosis is conferred through expression of a single EBV latent protein, the latent membrane protein LMP 1. Furthermore, we demonstrate that LMP 1 mediates this effect by up-regulating expression of the cellular oncogene bcl-2. The interplay between EBV infection and expression of this cellular oncogene has important implications for virus persistence and for the pathogenesis of virus-associated malignant disease.

Antigens, Viral↗
PubMed1990

Epstein-Barr virus latent membrane protein (LMP1) and nuclear proteins 2 and 3C are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23.

Latent Epstein-Barr virus (EBV) infection and growth transformation of B lymphocytes is characterized by EBV nuclear and membrane protein expression (EBV nuclear antigen [EBNA] and latent membrane protein [LMP], respectively). LMP1 is known to be an oncogene in rodent fibroblasts and to induce B-lymphocyte activation and cellular adhesion molecules in the EBV-negative Burkitt's lymphoma cell line Louckes. EBNA-2 is required for EBV-induced growth transformation; it lowers rodent fibroblast serum dependence and specifically induces the B-lymphocyte activation antigen CD23 in Louckes cells. These initial observations are now extended through an expanded study of EBNA- and LMP1-induced phenotypic effects in a different EBV-negative B-lymphoma cell line, BJAB. LMP1 effects were also evaluated in the EBV-negative B-lymphoma cell line BL41 and the EBV-positive Burkitt's lymphoma cell line, Daudi (Daudi is deleted for EBNA-2 and does not express LMP). Previously described EBNA-2- and LMP1-transfected Louckes cells were studied in parallel. EBNA-2, from EBV-1 strains but not EBV-2, induced CD23 and CD21 expression in transfected BJAB cells. In contrast, EBNA-3C induced CD21 but not CD23, while no changes were evident in vector control-, EBNA-1-, or EBNA-LP-transfected clones. EBNAs did not affect CD10, CD30, CD39, CD40, CD44, or cellular adhesion molecules. LMP1 expression in all cell lines induced growth in large clumps and expression of the cellular adhesion molecules ICAM-1, LFA-1, and LFA-3 in those cell lines which constitutively express low levels. LMP1 expression induced marked homotypic adhesion in the BJAB cell line, despite the fact that there was no significant increase in the high constitutive BJAB LFA-1 and ICAM-1 levels, suggesting that LMP1 also induces an associated functional change in these molecules. LMP1 induction of these cellular adhesion molecules was also associated with increased heterotypic adhesion to T lymphocytes. The Burkitt's lymphoma marker, CALLA (CD10), was uniformly down regulated by LMP1 in all cell lines. In contrast, LMP1 induced unique profiles of B-lymphocyte activation antigens in the various cell lines. LMP1 induced CD23 and CD39 in BJAB; CD23 in Louckes; CD39 and CD40 in BL41; and CD21, CD40, and CD44 in Daudi. In BJAB, CD23 surface and mRNA expression were markedly increased by EBNA-2 and LMP1 coexpression, compared with EBNA-2 or LMP1 alone. This cooperative effect was CD23 specific, since no such effect was observed on another marker, CD21.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, CD↗
PubMed1989

The gene for prolactin-inducible protein (PIP), uniquely expressed in exocrine organs, maps to chromosome 7.

The hormonally responsive prolactin-inducible protein (PIP) gene is expressed in benign and malignant breast tumor tissues and in such normal exocrine organs as sweat, salivary, and lacrimal glands. In this communication we report the regional chromosome localization of the PIP gene locus to chromosome 7 by Southern hybridization to DNA from human-hamster somatic cell hybrids, and to 7q32-36 by in situ hybridization.

Animals↗
PubMed1989

Two-compartment, two-sample technique for accurate estimation of effective renal plasma flow: theoretical development and comparison with other methods.

Discordance between effective renal plasma flow (ERPF) measurements from radionuclide techniques that use single versus multiple plasma samples was investigated. In particular, the authors determined whether effects of variations in distribution volume (Vd) of iodine-131 iodohippurate on measurement of ERPF could be ignored, an assumption implicit in the single-sample technique. The influence of Vd on ERPF was found to be significant, a factor indicating an important and previously unappreciated source of error in the single-sample technique. Therefore, a new two-compartment, two-plasma-sample technique was developed on the basis of the observations that while variations in Vd occur from patient to patient, the relationship between intravascular and extravascular components of Vd and the rate of iodohippurate exchange between the components are stable throughout a wide range of physiologic and pathologic conditions. The new technique was applied in a series of 30 studies in 19 patients. Results were compared with those achieved with the reference, single-sample, and slope-intercept techniques. The new two-compartment, two-sample technique yielded estimates of ERPF that more closely agreed with the reference multiple-sample method than either the single-sample or slope-intercept techniques.

Humans↗
PubMed1988

Epstein-Barr virus latent infection membrane protein alters the human B-lymphocyte phenotype: deletion of the amino terminus abolishes activity.

A latent infection membrane protein (LMP) encoded by the Epstein-Barr virus (EBV) genome in latently infected, growth-transformed lymphocytes alters the phenotype of a human EBV-negative B-lymphoma cell line (Louckes) when introduced by gene transfer. These LMP-expressing cells exhibit increased homotypic adhesion due to increased expression of the adhesion molecules LFA-1 and ICAM-1. Increased homotypic adhesion could foster B-cell growth by facilitating autocrine growth factor effects. LFA-3 expression is also induced. The induction of LFA-3 and ICAM-1 results in increased heterotypic adhesion to T lymphocytes. This could result in more effective T-cell immune surveillance. Since LMP is expressed in EBV-transformed lymphocytes and has been demonstrated to transform rodent fibroblasts in vitro, a wide range of possible effects on B-lymphoma cell growth were assayed. In the Louckes B-lymphoma cell line, EBV LMP causes increased cell size, acid production, plasma membrane ruffling, and villous projections. Although cell proliferation rate was not greatly affected, the steady-state intracellular free calcium level, transforming growth factor beta responsiveness, and expression of the lymphocyte activation markers (CD23 and transferrin receptor) were increased. Thus, LMP appears to be a mediator of EBV effects on B-cell transformation. In transfected lymphoma cells, LMP localizes to patches at the cell periphery and associates with the cytoskeleton as it does in EBV-transformed B lymphocytes or in rodent fibroblasts. A partially deleted form of LMP (D1LMP) does not aggregate in patches or associate with the cytoskeleton and had little effect on B-cell growth. Thus, cytoskeletal association may be integral to LMP activity.

Antibodies, Monoclonal↗
PubMed1987

Cytochemical profile of megakaryoblastic leukaemia: a study with cytochemical methods, monoclonal antibodies, and ultrastructural cytochemistry.

A cytochemical study using: Sudan black B; alpha-naphthyl acetate (ANAE) staining; estimation of alpha-naphthyl butyrate (ANBE) esterase activity; acid phosphatase activity; and 5' nucleotidase activity was carried out in 15 cases of megakaryoblastic leukaemia. These included cases of M7 acute myeloid leukaemia and blast crises of chronic granulocytic leukaemia. The megakaryoblastic nature of the blasts was first established using two monoclonal antibodies against platelet glycoproteins, and by estimating the platelet/peroxidase reaction at ultrastructural level. Our findings suggest that megakaryoblasts have a typical cytochemical profile comprising positive ANAE staining and acid phosphatase activity with a predominant localisation in the Golgi zone and negative or weak ANBE activity. A similar positive cytochemical pattern was also found in five cases of erythroleukaemia (M6). The specificity of the 5'nucleotidase activity for megakaryoblasts was not confirmed. In most cases of megakaryoblastic leukaemia there was no 5'nucleotidase activity only two cases showed positive reactions--reactions were positive in several cases of myeloblastic and lymphoblastic leukaemia. We suggest that cytochemical methods may be useful in diagnosing M6 and M7 acute leukaemia because less than 40% of leukaemic cells react with specific monoclonal antibodies.

5'-Nucleotidase↗
PubMed1987

Splenic B cell lymphoma with "villous" lymphocytes in the peripheral blood: a disorder distinct from hairy cell leukemia.

The clinical and laboratory features of 23 patients with a characteristic form of splenic lymphoma with circulating "villous" lymphocytes (SLVL) are described and compared with those of other B cell disorders with preferential splenic involvement. SLVL affects predominantly men in their early 70's and is characterized by gross splenomegaly with little or no lymphadenopathy, presence of monoclonal gammopathy in two thirds of the cases, and infiltration of the peripheral blood by lymphocytes with a characteristic pattern of membrane irregularity. These lymphocytes are often confused with cells from hairy cell leukemia, from which they can be distinguished by a number of morphological features, by having a small cell volume, and by lack of expression of the HC2 and Tac antigens. The bone marrow is easily aspirated in the majority of cases and shows a relatively sparse infiltration. The spleen histology shows predominant white pulp involvement, although infiltration of the red pulp is seen in a small number of cases. The differential diagnosis of SLVL should also include hairy cell leukemia variant, prolymphocytic leukemia, and atypical forms of chronic lymphocytic leukemia.

Aged↗
PubMed1986

Results of radiotherapy for stage II testicular seminoma.

Of 53 patients with Stage II seminoma treated with radiotherapy between 1970 and 1984, 9 (17%) relapsed, 5 (9%) died of testicular cancer and 1 (2%) died of intercurrent disease. Relapse rates for IIA, IIB and IIC were 11, 18 and 28% respectively. Supradiaphragmatic irradiation was not advantageous; of 22 patients receiving infradiaphragmatic irradiation, 3 (14%) relapsed, compared with 6/31 (19%) of those who had supra- and infradiaphragmatic irradiation. Despite the radioresponsiveness of seminoma, 50% of IIC patients had residual masses 4 months after radiotherapy and 20% at one year, however, this finding did not predict eventual outcome. Serum human chorionic gonadotrophin (HCG) levels were raised prior to radiotherapy in 3/26 (11.5%) Stage IIA and IIB patients and 3/10 (30%) IIC patients. However, this did not influence the outcome of radiotherapy since only 0/6 patients with raised HCG levels relapsed compared with 7/30 (23%) of those with normal levels. Analysis of the pattern of relapse together with the fact that 2/6 patients who had the extent of tumour defined at laparotomy and/or who had total abdominal irradiation relapsed, suggests that further refinement of radiotherapy is unlikely to improve the results of treatment for IIC patients and that chemotherapy should be considered the treatment of choice.

Dysgerminoma↗
PubMed1985

Purification and preliminary characterization of the glycoprotein Ib complex in the human platelet membrane.

Human platelet glycoprotein Ib (GP Ib) is a major integral membrane protein that has been identified as the platelet-binding site mediating the factor VIII/von Willebrand-factor-dependent adhesion of platelets to vascular subendothelium. Recent evidence suggests that GP Ib is normally complexed with another platelet membrane protein, GP IX. In this study, human platelet plasma membranes were selectively solubilized with a buffer containing 0.1% (v/v) Triton X-100. The GP Ib complex (GP Ib plus GP IX) was purified to homogeneity in approximately 30% yield by immunoaffinity chromatography of the membrane extract using the anti-(glycoprotein Ib complex) murine monoclonal antibody, WM 23, coupled to agarose. GP Ib and GP IX were subsequently isolated as purified components by immunoaffinity chromatography of the GP Ib complex using a second anti-(glycoprotein Ib complex) monoclonal antibody, FMC 25, coupled to agarose. As assessed by dodecyl sulphate/polyacrylamide gel electrophoresis, purified GP Ib was identical to the molecule on intact platelets and had an apparent relative molecular mass of 170 000 under nonreducing conditions and 135 000 (alpha subunit) and 25 000 (beta subunit) under reducing conditions. GP IX had an apparent Mr of 22 000 under both nonreducing and reducing conditions. Purified Gb Ib complex and GP Ib inhibited the ristocetin-mediated, human factor VIII/von Willebrand-factor-dependent and bovine factor VIII/von Willebrand-factor-dependent agglutination of washed human platelets suggesting the proteins had been isolated in functionally active form. GP Ib alpha had a similar amino acid composition to that previously reported for its proteolytic degradation product, glycocalicin. The amino acid compositions of GP Ib beta and GP IX were similar but showed marked differences in the levels of glutamic acid, alanine, histidine and arginine. The N-termini of GP Ib alpha and GP IX were blocked; GP Ib beta had the N-terminal sequence, Ile-Pro-Ala-Pro-. On crossed immunoelectrophoresis, both GP Ib and GP IX were found to occur in the same immunoprecipitin arc(s) whether the platelets had been solubilized in the absence or presence of the calcium-dependent protease inhibitor, leupeptin. Binding studies in platelet-rich plasma indicated a similar number of binding sites (means +/- SD) for three anti-(glycoprotein Ib complex) monoclonal antibodies: AN 51, epitope on GP Ib alpha (22 000 +/- 2700, n = 3), WM 23, epitope on GP Ib alpha (21 000 +/- 3400, n = 3), FMC 25, epitope on GP IX (20 100 +/- 2700, n = 3), and FMC 25 (Fab')2 (27 100 +/- 800, n = 2).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1983

Delay in diagnosis of adult coeliac disease.

The delay in diagnosis of 106 patients with adult coeliac disease, diagnosed between 1976 and 1980, was studied. Overall, delay in diagnosis was 11 +/- 10.6 years, being considerably greater in females (12.8 +/- 7.8 years) than in males (3.5 +/- 9.8 years). Most of this delay occurred prior to hospital referral, although that following referral to hospital clinics was still significant (1.8 +/- 4.8 years). The most common presenting complaints were lassitude (75%) anaemia (65%) and flatulence (50%). Typical gastro-intestinal symptoms were relatively uncommon and mild, but when present led to a more speedy diagnosis. It is concluded that, despite advances in modern diagnostic procedures, little progress has been made in hastening the diagnosis of coeliac disease.

Aged↗