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Biomedical subjects

S Gregory

Publications and source records attributed to S Gregory.

At least 55 records · Page 3Linked to original sources
PubMed1995

Which depressed patients respond to ECT? The Nottingham results.

The Nottingham electroconvulsive therapy (ECT) trial was designed with a simulated treatment group to test prospectively the power of delusions or agitation to predict response. The response of patients without retardation and without delusions was examined retrospectively as well because of doubts over the usefulness of ECT for this subgroup. Deluded/nondeluded and agitated/nonagitated subtypes responded significantly to real treatment. Neither delusions nor agitation predicted greater treatment response. Patients without retardation, with or without delusions responded to real ECT, supporting the continuing prescription of ECT for these patients as well.

Adult↗
PubMed1995

Simultaneous assessment of cell kinetics and programmed cell death in bone marrow biopsies of myelodysplastics reveals extensive apoptosis as the probable basis for ineffective hematopoiesis.

Despite hypercellular bone marrows (BM), peripheral cytopenias are the rule in patients with myelodysplastic syndromes (MDS). This study examined the roles played by cell birth and cell death rates in generating this paradox. Cell kinetics from BM biopsies of 35 MDS patients were measured using intravenous infusions of either iododeoxyuridine or bromodeoxyuridine, or both. Degree of apoptosis or programmed cell death (PCD) was estimated using in situ end-labeling of DNA directly from BM biopsies, which were simultaneously double-labeled from proliferation/PCD. MDS were found to be highly proliferative disorders with large numbers of myeloid, erythroid, and megakaryocytic cells synthesizing DNA. Median cycling time (Tc) of myeloblasts was more rapid than that of patients with acute myeloid leukemia (44.1 hr vs. 56.0 hr). Interestingly, most marrow cells of all three lineages in 32 of 34 evaluable cases were undergoing PCD. In 19 of 32 patients, greater than 75% cells were apoptotic. Surprisingly, large numbers of S-phase cells were found to be simultaneously undergoing PCD, as were stromal cells of the BM microenvironment. We conclude that the extensive apoptosis in hematopoietic cells effectively cancels the high birth rate resulting in ineffective hematopoiesis and accounting for deficient bone marrow function.

Acute Disease↗
PubMed1995

Mediation of inflammation by cyclooxygenase-2.

Non-steroidal antiinflammatory drugs (NSAIDs) are commonly used for the treatment of inflammation, pain, and fever. Mechanistically, these compounds are believed to act via inhibition of the enzyme cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid to the prostaglandins (PGs). Although commercially available NSAIDS are efficacious antiinflammatory agents, significant side effects limit their use. Recently two forms of COX were identified- a constitutively expressed COX-1 and a cytokine-inducible COX-2. Commercially available NSAIDs like indomethacin inhibit both COX-1 and COX-2 suggesting the hypothesis that toxicities associated with NSAID therapy are due to inhibition of the non-regulated or constitutive form of COX (COX-1) in normal tissues, whereas therapeutic benefit derives from inhibition of the inducible enzyme, COX-2, at the site of inflammation. Therefore, a selective inhibitor of COX-2 may be anti-inflammatory without GI toxicity-providing a significant improvement over currently available NSAIDs.

Animals↗
PubMed1995

A multivariate study of non Hodgkin's lymphoma involving proliferation, apoptosis, bcl-2 and the microenvironment.

The study was carried out on 22 patients with non-Hodgkin's lymphoma (NHL) who had received sequential infusions of two thymidine analogues iododeoxyuridine (IUdR) and bromodeoxyuridine (BrdU). Cell cycle kinetic studies seemed to differentiate distinctly between low grade lymphoma (n = 8, LI = 2.6%) compared to that of intermediate grade (n = 9, LI = 13%, p = 0.0001) and high grade NHL (n = 5, LI = 16.3%, p = 0.0062). While the majority of 14 intermediate and high grade lymphomas had a high labeling index there were 3/14 patients with a LI of 5.5%, 5.5% and 4.1% respectively. A decrease in the rate of programmed cell death (PCD) or apoptosis due to the overexpression of bcl-2 has been implicated as the possible pathogenesis for follicular lymphoma. We determined the presence of bcl-2 protein immunohistochemically and apoptosis by in situ end labeling of DNA which detects cells in early stages of PCD not recognized morphologically. Nine NHL patients demonstrated PCD ranging from 1%-40%, while it was undetectable in 13/22 patients. Of these 13 cases, 6 showed the presence of bcl-2 expression. To understand the relationship of the microenvironment to the lymphoma cells, the presence of transforming growth factor beta (TGF-beta) was determined immunohistochemically. TGF-beta was present in all the cases where bcl-2 was present, except one. This study highlights some of the key biological features of NHL cells and their microenvironment.

Apoptosis↗
PubMed1995

A new look at OEM (original equipment manufacturer) service agreements.

Next to personnel services, equipment maintenance is the second largest budgetary expense in large radiology departments. Because they are under constant pressure to contain costs, radiology administrators spend considerable time negotiating the best service at the lowest cost. Today, administrators have several options for imaging equipment maintenance: equipment maintenance insurance, in-house engineering, and various arrangements with original equipment manufacturers (OEMs) and independent service organizations (ISOs). In response to increased competition, OEMs have become more price-competitive with ISOs and have expanded their service menu and equipment maintenance insurance programs. OEM service menu options include: full service, tiered pricing, labor only, planned maintenance, full service with deductible, shared maintenance and extended warranty. Any type of service arrangement can be customized according to equipment age and sophistication, redundancy, income-producing potential, criticality of downtime and the strength and depth of the service organization. Even when vendor maintenance contracts are more expensive than purchasing service on a time-and-materials basis, they allow customers to budget accurately for the service of covered equipment. The authors' institution gets the best results for the best price from a judicious mix of maintenance options. Wise customers will explore many options before choosing a service agreement.

Budgets↗
PubMed1994

Analysis of the regulation of the Aspergillus nidulans acuD gene, encoding isocitrate lyase, by construction of a hybrid promoter.

In order to confirm functionally that a 208 bp fragment of the 5'-flanking sequence of the acuD gene of Aspergillus nidulans is the region responsible for acetate inducibility and catabolite repression, a hybrid promoter was constructed by insertion of this fragment into the promoter of the (highly expressed) oliC gene of A. nidulans. Analysis of expression of the lacZ reporter gene fused to the oliC/acuD promoter showed induction by acetate at much higher levels than wild-type acuD expression. Acetate inducibility of the hybrid promoter was dependent on the facB gene, demonstrating that a facB-dependent upstream activating sequence (UAS) for acetate must be located in the 208 bp acuD fragment. In parallel, partial relief of the transcriptional repression of acetate inducibility by sucrose and glucose was observed in a creA- background, showing that the 208 bp acuD fragment also responds to the creA gene. In addition, the results show that combination of a regulatory element from a low-expression promoter (acuD) with a high-expression constitutive promoter (oliC) leads to amplification of the level of regulated expression.

Acetates↗
PubMed1994

An integrated physical map of 210 markers assigned to the short arm of human chromosome 11.

Using a panel of patient cell lines with chromosomal breakpoints, we constructed a physical map for the short arm of human chromosome 11. We focused on 11p15, a chromosome band harboring at least 25 known genes and associated with the Beckwith-Wiedemann syndrome, several childhood tumors, and genomic imprinting. This underlines the need for a physical map for this region. We divided the short arm of chromosome 11 into 18 breakpoint regions, and a large series of new and previously described genes and markers was mapped within these intervals using fluorescence in situ hybridization. Cosmid fingerprint analysis showed that 19 of these markers were included in cosmid contigs. A detailed 10-Mb pulsed-field physical map of the region 11p15.3-pter was constructed. These three different approaches enabled the high-resolution mapping of 210 markers, including 22 known genes.

Beckwith-Wiedemann Syndrome↗
PubMed1994

Non-epileptic attack disorder: a clinical audit.

The results of an audit of all patients with non-epileptic attack disorder admitted over a 1-year period to a neuropsychiatry tertiary referral centre are presented. The high incidence of: sexual abuse, previous psychiatric history and previous brain injury is noted. Reference is made to the reaction of patients and relatives to disclosure of the diagnosis and the management difficulties which this group of patients pose. The different underlying psychopathological processes are discussed and it is suggested that the diagnosis of NEAD, purely by the exclusion of epilepsy, might carry the risk of treating these patients as a homogenous group. An eclectic approach by an experienced, multi-disciplinary team is probably the most appropriate way of successfully managing the condition.

Counseling↗
PubMed1994

Novel in situ double labeling for simultaneous detection of proliferation and apoptosis.

We describe a novel double-labeling method to simultaneously investigate proliferation and apoptosis from plastic-embedded biopsy specimens (PEBs). Infusions of bromo- and/or iododeoxyuridine (BrdU/IudR) were given to 10 patients, five with acute myeloid leukemia (AML) and five with myelodysplastic syndromes (MDS), and S-phase cells were measured in PEBs using a monoclonal anti-IudR/BrdU antibody. Apoptosis was measured by in situ end-labeling (ISEL) of DNA. The results demonstrate that both AML and MDS are highly proliferative disorders but that there is almost no apoptosis in the former, whereas extensive apoptosis was observed in the latter. Double labeling revealed that large numbers of S-phase cells in MDS were simultaneously undergoing apoptosis. We conclude that the high cell death in MDS cancels the high cell birth, resulting in a functionally aplastic marrow and thus accounting for the observed ineffective hematopoiesis. On the other hand, AML is rapidly fatal, probably owing to high cell birth with no or minimal cell death. Therapeutic strategies to prevent intramedullary programmed cell death of hematopoietic precursors should be evaluated in MDS, and efficacy of chemotherapy in AML can be assessed by measuring the induction of apoptosis in post-treatment biopsy specimens.

Acute Disease↗
PubMed1993

Genes for interleukin 7 are transcribed in leukemic cell subsets of individuals with chronic lymphocytic leukemia.

Regulation of expression of interleukin 7 (IL-7) mRNA is aberrant in the leukemic subset of cells of chronic lymphocytic leukemia (CLL) patients. The entire coding sequence for IL-7 as well as an alternatively spliced IL-7 mRNA are transcribed in these leukemic cells. No IL-7 mRNA expression is detected in fresh peripheral blood mononuclear cells from normal individuals. Furthermore, the "normal" nonleukemic subsets of cells isolated from the same CLL patients also do not express IL-7 mRNA. The only subset of cells in which IL-7 mRNA is detected is the one that contains the leukemic cells themselves. The polymerase chain reaction was used to examine cytokine expression, and flow cytometry was used to purify the various subsets of peripheral blood mononuclear cells examined in these studies, as well as to examine IL-7 receptor expression. A proportion of the cells from the CLL patients express receptors that are capable of binding IL-7, whereas T cell-depleted normal cell preparations do not express receptors for IL-7 that are detectable with IL-7 fluorokines. The IL-7 receptor-bearing cells in CLL patients include a portion of leukemic cells and a fraction of the T cells, as well as some non-T, non-B cells. These findings suggest that IL-7 and IL-7 receptor expression in CLL may be relevant not only to growth regulation of the leukemic cells but to the immunological abnormalities that occur in the disease as well, possibly via the induction of inappropriate immune activity of IL-7 receptor-bearing cells.

Adult↗
PubMed1993

A VM 26-based regimen for patients with previously untreated non-Hodgkin lymphoma. Prolonged disease-free survival in patients younger than 60 years of age: a phase II trial of the eastern Cooperative Oncology Group.

BACKGROUND: The epidophyllotoxin VM 26 has been shown to have single-agent activity in patients with diffuse aggressive lymphoma. In an attempt to determine its activity in combination with other agents known to be effective in lymphoma, a Phase II trial of a novel chemotherapy regimen was conducted. METHODS: Forty-two patients with Stages II, III, and IV diffuse aggressive lymphoma were treated with teniposide, doxorubicin, prednisone, cyclophosphamide, vincristine, and bleomycin (PA Ten-CPOB) as part of a Phase II trial of the Eastern Cooperative Oncology Group. Fifty-five percent of patients had Stage IV disease, 21% Stage III, and 24% Stage II. RESULTS: The overall complete response rate was 64%. Of the 27 patients who had complete response, 19 (70% [45% of the entire group]) are still alive without disease (median follow-up, 5.7 years). No patient had a follow-up time of less than 5 years. On examination of factors that were predictive of survival and relapse, it was found that age younger than 60 years was predictive of long-term survival, as 76% of patients younger than 60 years of age were alive without disease. Forty patients were evaluable for toxicity. There were four (10%) early deaths, and six patients (15%) had Grade 4 hematologic toxicity. CONCLUSIONS: This alternating combination chemotherapy regimen (PA Ten-CPOB) results in a complete response rate comparable to what has been reported previously in the literature, but 45% of patients in this series demonstrated long-term disease-free survival. When patients younger than 60 years of age with follow-up times of at least 5 years were considered, disease-free survival was 76%.

Adult↗
PubMed1993

T cell lymphokine-induced secretion of cytokines by monocytes from patients with multiple sclerosis.

To investigate the function of peripheral blood monocytes in multiple sclerosis (MS), we measured the production of the cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interleukin-6 (IL-6), and the procoagulant, tissue factor (TF) in 17 patients with chronic progressive MS and 15 normal controls. Monocyte activity was tested under unstimulated, minimal endotoxin conditions and after culture with various stimuli, including Escherichia coli lipopolysaccharide (LPS), crude supernatant from anti-CD3-activated T cells, recombinant interleukin-2 (rIL-2), and recombinant interferon-gamma (rIFN-gamma). A higher number of MS patients than controls had circulating monocytes which spontaneously secreted IL-6 or contained detectable cell-associated IL-1 beta. Monocyte responses to LPS were comparable between the two groups; LPS caused production and secretion of all cytokines and TF in every MS patient and control. In contrast, crude T cell supernatants, rIL-2, and rIFN-gamma induced IL-1 beta release in a higher number of MS monocytes than that in controls, whereas the production and secretion of the other cytokines and TF activity were similar between the groups. We conclude that some MS patients have "primed" circulating monocytes, as shown by excessive spontaneous IL-6 release and intracellular IL-1 beta synthesis. Unstimulated MS monocytes, however, are not different from controls with respect to spontaneous secretion of small amounts of IL-1 beta and TNF alpha and expression of cell surface TF. Excessive IL-1 beta secretion by MS monocytes after stimulation with T-cell-derived lymphokines suggests dysregulation of T cell-monocyte interactions which may be most relevant in the central nervous system plaques where activated T cells are found.

Humans↗
PubMed1993

HIV-1 pseudotype virus containing a Cocal virus genome and an HIV envelope: construction, assay and use.

A method is described for the production and assay of pseudotype viruses between human immunodeficiency virus type 1 (HIV-1) and Cocal virus (COV), containing an HIV-1 envelope and a COV genome (COV(HIV)). COV(HIV) pseudotype virus is a useful tool for the investigation of a variety of questions regarding HIV entry into susceptible cells, including steps in virus binding, fusion, and internalization, and the role of molecules which inhibit entry. COV, a rhabdovirus closely related to vesicular stomatitis virus (VSV), replicated and caused cytopathic effect in primary cultures of human peripheral blood lymphocytes (PBLs) and monocyte-derived macrophages (MDM), and in human cell lines of lymphocytoid or monocytoid origin, making it an ideal candidate for pseudotype production. 174XCEM cells, which were permissive for selected macrophage-tropic strains as well as most lymphocyte-tropic strains of HIV-1, were used to produce stocks of putative pseudotype virus. To neutralize parental COV in these stocks, a rabbit antiserum was produced which had a neutralization index of > 10(7) at a dilution of 1:100. Using these methods, pseudotype viruses were produced with a titer of about 10(4) PFU per ml; these same stocks contained HIV-1 at a titer of about 10(5) TCD50 per ml and COV at a titer of about 10(8) PFU per ml. CD4-expressing HeLa cells were used to assay pseudotype stocks made with lymphocyte-tropic strains of HIV-1. The authenticity of the pseudotype stocks was validated by several controls, including their failure to register on congenic CD4-negative HeLa cells and their inhibition by monoclonal anti-CD4 antibodies such as Leu 3a.

Animals↗
PubMed1993

Women defining health: food, diet and body image.

This article explores the relationship between gender and food through analysing data obtained from a series of women-only discussion groups, the participants of which explored self definitions of the term 'health'. What is distinct about this data, collected in the North East of England, is the clear link respondents perceive between food, diet and health. However, due to a number of factors such a knowledge may not result in dietary and ultimately bodily change. The many implications of such findings for health education are outlined in the discussion section of the paper.

Adult↗
PubMed1993

Computer-aided administration of a radiology equipment insurance program.

The Medical College of Georgia's radiology department has developed computer software that helps the department manage its radiology equipment insurance program. By providing clear menus and choice boxes instead of manual typing wherever possible, the software minimizes the time spent on data entry and management functions. In addition, the software helps track vendor invoices and unreimbursed claims, and maintains a service call log. It also provides a bar-coded service ticket for use by in-house engineers. Completed tickets, which are copied and filed, have replaced ledger books. Furthermore, the software helps the department comply with JCAHO requirements, since service tickets link the documentation of quality control problems to their resolution.

Academic Medical Centers↗
PubMed1992

Cytokines in the vitreous of patients with proliferative diabetic retinopathy.

Sixteen vitreous and paired serum samples from 13 patients with proliferative diabetic retinopathy, vitreous samples from seven cadaveric control subjects, and aqueous humor samples from 15 normal control subjects were assayed for the cytokines interleukin-1, tumor necrosis factor-alpha, interleukin-6, and interferon-gamma. Interleukin-6 was detected in 15 of 16 vitreous samples (94%) from diabetic patients, but it was not detected in any of the aqueous humor samples. Vitreous interleukin-6 levels positively correlated with ocular disease activity. Interleukin-1 was detected in seven of 16 vitreous samples (44%) and in four of ten aqueous humor samples (40%), whereas tumor necrosis factor-alpha and interferon-gamma were never detected in vitreous or aqueous fluid. Serum samples from diabetic patients and control subjects contained comparable low levels of interleukin-6. Interleukin-1, tumor necrosis factor-alpha, and interferon-gamma were not found in any of the sera. Because interleukin-6 can function as B-cell differentiation factor, this cytokine may have a role in immunoglobulin deposition in the ocular tissues and in the immunopathologic characteristics of proliferative retinopathy.

Adult↗