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M Collins

Publications and source records attributed to M Collins.

At least 73 records · Page 4Linked to original sources
PubMed1998

A far upstream, cell type-specific enhancer of the mouse thrombospondin 3 gene is located within intron 6 of the adjacent metaxin gene.

Thrombospondin 3 (TSP3) is a secreted, pentameric glycoprotein whose regulation of expression and function are not well understood. Mouse Thbs3 is located just downstream from the divergently transcribed metaxin gene (Mtx), which encodes an outer mitochondrial membrane import protein. Although Thbs3 and Mtx share a common promoter region, previous studies showed that Mtx is regulated by proximal elements that had little effect on Thbs3 expression. In this study, transient transfection of rat chondrosarcoma cells and NIH-3T3 fibroblasts demonstrated that Thbs3 is regulated in a cell type-specific manner by a position- and orientation-independent far upstream enhancer located within intron 6 of Mtx. Despite its greater proximity to the transcription start site of Mtx, the Thbs3 enhancer did not have a significant effect on Mtx expression. Two DNA-protein complexes, which were both required for activity, were identified when nuclear extracts were assayed with a probe containing the enhancer sequence. The protein in one of these complexes was identified as Sp1, while the other DNA-protein complex remains uncharacterized. A 6-kilobase pair promoter containing the enhancer was able to direct specific expression of the E. coli lacZ gene in transgenic mice, whereas a 2-kilobase pair promoter that lacked the enhancer was inactive. Thus, despite their close proximity, the genes of the Mtx/Thbs3 gene cluster are regulated independently.

3T3 Cells↗
PubMed1998

Retroviral vector targeting to melanoma cells by single-chain antibody incorporation in envelope.

Two strategies for targeting recombinant retroviruses to melanoma cells were compared. One was to extend the tropism of an ecotropic envelope to human melanoma cells, the other was to enhance the tropism of an amphotropic envelope for melanoma cells. Chimeric retroviral envelopes, incorporating a single-chain antibody (ScFv) directed against high-molecular-weight melanoma-associated antigen (HMWMAA) at the amino terminus are correctly processed and incorporated into virions. ScFv-ecotropic envelope chimeras allow specific, but low-titer, targeting of HMWMAA-positive cells, when co-expressed with ecotropic envelopes. ScFv-amphotropic envelope chimeras bind specifically to HMWMAA-positive cells and allow preferential infection at high titer.

Amino Acid Sequence↗
PubMed1998

Hepatitis G virus infection in patients transplanted for cryptogenic cirrhosis: red flag or red herring?

BACKGROUND: The significance of hepatitis G (HGV) infection in liver transplant recipients is not known. We set out to determine the pre-orthotopic liver transplantation (OLT) prevalence, the pre- and postoperative viral titers of HGV, and the allograft histology in patients infected with HGV who underwent OLT for cryptogenic cirrhosis. METHODS: HGV RNA was measured using a research-based branched DNA assay. The assay used a target-specific probe set that was based on the 5'-untranslated region of the HGV genome. Allograft histology was assessed with protocol liver biopsies in all patients who survived longer than 6 months. RESULTS: The preoperative prevalence of HGV infection in recipients transplanted for cryptogenic cirrhosis was 26%. Thirty-seven percent (12 of 33) of recipients who had serum available in the first postoperative month had HGV infection. Mean HGV RNA levels were 9.8 (+/-4.2) (viral molecular equivalents/ml x 10[6]) before OLT and 37.5 (+/-10.7) at 1 year after OLT. In 4 of the 11 cryptogenic recipients in whom HGV RNA was detectable in the first postoperative month, HGV RNA fell to undetectable levels at the most recent follow-up (mean 70 months). Of the five cryptogenic recipients who continue to have measurable HGV RNA, three have unexplained hepatitis histologically. CONCLUSIONS: These findings suggest the following: 1) The prevalence of HGV infection in patients undergoing OLT for cryptogenic cirrhosis is about 25%. 2) In recipients persistently infected with HGV, mean HGV RNA titers increase after OLT. 3) HGV RNA becomes undetectable in about one third of recipients who had detectable HGV RNA in the first month after OLT. 4) Hepatitis of uncertain etiology occurs in 60% (3 of 5) of persistently HGV-infected cryptogenic recipients.

Adult↗
PubMed1998

Heteroclitic proliferative responses and changes in cytokine profile induced by altered peptides: implications for autoimmunity.

Productive engagement of T cell receptors (TCRs) by cognate ligand (major histocompatibility complex plus peptide) leads to proliferation, differentiation, and the elaboration of effector functions. Altered peptides generated by single amino acid substitutions in the antigenic peptide have diverse effects on the outcome of the T cell response. We have generated an altered peptide (Q144) from an autoantigenic peptide of myelin proteolipid protein 139-151 by a single amino acid substitution (from tryptophan to glutamine) in the primary TCR contact at position 144 that is capable of inducing CD4(+) T cell responses in H-2(s) mice. By using a Q144-specific T cell clone (Q1.1B6), we see a hierarchy in T cell proliferation and cytokine production with various position 144 substituted peptides and have identified a peptide (L144) that hyperstimulates this T cell clone. In contrast to Q144, L144 induces maximal proliferation at 7 logs lower antigen concentration, induces greater cell death at higher antigen dose, and induces the secretion of cytokines not detected following stimulation with the cognate ligand. This heteroclitic T cell response associated with changes in cytokine profile was observed with several other T cell clones of different specificities. The L144 peptide also induces costimulation independent proliferation and cytokine production from the Q1.1B6 T cell clone. We describe this as a superagonist response. Such responses may have a role in the initiation of autoimmunity by promoting a proinflammatory environment following ligation of a cross-reactive TCR on autoreactive T cells.

Amino Acid Sequence↗
PubMed1998

Quantitation of hepatitis G and C viruses in the liver: evidence that hepatitis G virus is not hepatotropic.

Hepatitis G virus (HGV) is prevalent in patients with chronic liver disease and has been previously detected in liver specimens. However, it is unknown whether the virus is replicating in the liver or is simply a contaminant from serum. We sought to determine whether HGV was hepatotropic and to determine whether coinfection with HGV and hepatitis C virus (HCV) influenced the level of either virus. Virus was quantitated using branched DNA (bDNA) assay for both HGV and HCV in the liver explants and pretransplant serum samples from 30 transplant recipients: Group I, HGV/HCV coinfection (n = 10); group II, HCV infection alone, (n = 8); group III, HGV alone (n = 12). In patients with coinfection HCV (RNA) titers in liver were consistently higher than those for HGV RNA (median 1.13 x 10(8) and 360,000 Eq/g respectively, P < .01). The ratio of liver/serum viral RNA was significantly higher for HCV than for HGV (median 129 and 0.3 respectively, P < .01). Levels of HCV RNA were similar in patients with HCV infection alone versus those with HGV/HCV coinfection (median; liver = 1.15 x 10(7) vs. 1.13 x 10(8) Eq/g, serum = 500,000 vs. 200,000 Eq/mL) and levels of HGV RNA in liver and serum were similar in patients with HGV infection alone compared to those with HGV/HCV coinfection (median; liver = 1.2 x 10(6) vs. 4.0 x 10(5) Eq/g, serum = 4.5 x 106 vs. 2.6 x 10(6) Eq/mL). Levels of either virus appeared unaffected by the presence of an additional virus. The high ratio of HCV RNA levels in liver compared to serum is consistent with its known hepatotropism, but this pattern was not observed for HGV. The median liver/serum ratio of HGV RNA was less than unity, a finding consistent with serum contamination of liver tissue. Thus we conclude that the liver is not the main site of HGV replication.

Flaviviridae↗
PubMed1998

Interhemispheric communication is via direct connections.

Two priming experiments, using normal university students as subjects, independently projected low imagery primes and concrete target words to the left or right visual fields (LVF or RVF) to examine the merits of three spreading activation models of interhemispheric communication: (i) callosal relay of a semantically encoded prime; (ii) transfer of products activated as a result of the spread of activation; and (iii) direct connections between the hemispheres. The first experiment temporally separated pairs by a stimulus onset asynchrony (SOA) of 250 ms and obtained strong support for the direct connections model. Priming effects were obtained only when the prime was projected to the RVF and the target to the LVF. The pattern of priming effects suggested that low imagery words projected to the left hemisphere can activate concrete associates in the right hemisphere via direct callosal connections between the two. In the second experiment, the SOA was increased to 450 ms. This time, RVF-RVF priming was obtained along with RVF-LVF priming. The findings are interpreted within a modification of Bleasdale's (1987) framework, where abstract/low imagery words and concrete/high imagery words are represented in separate subsystems in the left hemisphere lexicon. Support was also found for the view that the left hemisphere is comprised of a complex network of abstract and concrete words, while the right hemisphere operates as a subsidiary word processor, subserving linguistic processing with a limited, special purpose lexicon comprised of associative connections between concrete, imageable words (e.g., Zaidel, 1983a; Bradshaw, 1980). Interhemispheric communication in the priming procedure appears to occur at the semantic level, via direct connections between the hemispheres.

Adult↗
PubMed1998

Obstetrician-gynecologists as primary care physicians: the Oregon experience--early perceptions regarding the effects of legislative action.

OBJECTIVE: Our purpose was to assess whether legislative action influenced the role of obstetrician-gynecologists as primary care physicians. STUDY DESIGN: An observational study was performed on the basis of a questionnaire sent to 410 obstetrician-gynecologists and 27 medical directors of managed-care organizations. RESULTS: Of 67% of obstetrician-gynecologists and 96% of medical directors who responded, there was agreement as to the content of primary care, but a minority (38%) of obstetrician-gynecologists identified themselves as primary care providers. A minority of medical directors (35%) felt that obstetrician-gynecologists should serve in that role. Both obstetrician-gynecologists and medical directors felt that legislation had little impact. CONCLUSION: The reticence of obstetrician-gynecologists to assume a major role in primary care appears to be the result of an uneasiness with accepting a more comprehensive role in patient management and gatekeeping. They appear comfortable with the more traditional roles but feel that training and experience has not prepared them well for the management of more complex medical problems.

Female↗
PubMed1998

Control of hepatitis B in the United Kingdom.

Control of hepatitis B in the UK is based upon selective vaccination of persons in high-risk groups. To assess the likely cost-effectiveness of changes to this policy, information on the current burden of HBV infection in the UK is required. Laboratory reports of acute hepatitis B suggest that the vast majority of new hepatitis B infections acquired in the UK occur in adults, even after adjustment for unapparent infection. In childhood, perinatal transmission remains the most significant known risk factor. Universal antenatal screening has the potential to prevent perinatal infections in UK births and a substantial proportion of those UK acquired infections which lead to carriage. In addition, to antenatal screening, universal infant vaccination (at 2, 3 and 4 months) can, in the short term, only prevent the small number of infections acquired in childhood. Economic analysis using current surveillance data is required to assess the possible cost-benefit of universal vaccination. Regardless of this, there is an urgent need to improve selective vaccination and to ensure that a high proportion of antenatal carriers is identified.

Acute Disease↗
PubMed1998

IL-13, IL-4Ralpha, and Stat6 are required for the expulsion of the gastrointestinal nematode parasite Nippostrongylus brasiliensis.

Although IL-4 induces expulsion of the gastrointestinal nematode parasite, Nippostrongylus brasiliensis, from immunodeficient mice, this parasite is expelled normally by IL-4-deficient mice. This apparent paradox is explained by observations that IL-4 receptor alpha chain (IL-4Ralpha)-deficient mice and Stat6-deficient mice fail to expel N. brasiliensis, and a specific antagonist for IL-13, another activator of Stat6 through IL-4Ralpha, prevents worm expulsion. Thus, N. brasiliensis expulsion requires signaling via IL-4Ralpha and Stat6, and IL-13 may be more important than IL-4 as an inducer of the Stat6 signaling that leads to worm expulsion. Additional observations made in the course of these experiments demonstrate that Stat6 signaling is not required for IL-4 enhancement of IgG1 production and actually inhibits IL-4-induction of mucosal mastocytosis.

Animals↗
PubMed1998

Clinical safety of oral sildenafil citrate (VIAGRA) in the treatment of erectile dysfunction.

Sildenafil citrate has been shown to be effective in a wide range of patients with erectile dysfunction and has been approved in the United States for this indication. The overall clinical safety of oral sildenafil, a potent inhibitor of phosphodiesterase type 5, in the treatment of erectile dysfunction was evaluated in more than 3700 patients (with a total of 1631 years of exposure worldwide). Safety and tolerability data were analysed from a series of double-blind, placebo-controlled studies and from 10 open-label extension studies of sildenafil in the treatment of erectile dysfunction. A total of 4274 patients (2722 sildenafil, 1552 placebo; age range 19-87 y) received double-blind treatment over a period of up to six months' duration, and 2199 received long-term, open-label sildenafil for up to 1 y. The most commonly reported adverse events (all causes) were headache (16% sildenafil, 4% placebo), flushing (10% sildenafil, 1% placebo), and dyspepsia (7% sildenafil, 2% placebo) and they were predominantly transient and mild or moderate in nature. These adverse events reflect the pharmacology of sildenafil as a phosphodiesterase type 5 inhibitor. No cases of priapism were reported. The rate of discontinuation due to adverse events (all causes) was comparable for patients treated with sildenafil (2.5%) and placebo (2.3%). In open-label extension studies, 90% of patients completed long-term sildenafil treatment, with only 2% withdrawing due to adverse events. Sildenafil is a well-tolerated oral treatment for erectile dysfunction.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1998

Screening and chemoprophylaxis for tuberculosis infection in college populations.

Active tuberculosis and the potential for widespread disease exist on college campuses. To maximize the benefit and minimize the potential harm of a screening program, health service clinicians should administer tuberculin skin tests to high-risk students only. Those found to be infected should be considered for prophylactic treatment. The criteria that identify students as being at high risk need to be clearly appreciated, especially the issue of birth outside the United States. Certain countries of origin pose a high risk; others do not. By understanding the fundamentals of the current pandemic and employing a consistent approach, college health professionals can make the correct screening decisions, thereby reducing the risk to their campus communities and assisting in the eradication of this preventable disease.

Chemoprevention↗
PubMed1998

Recombinant human interleukin-11 does not affect functions of purified human neutrophils in vitro.

Recombinant human interleukin-11 (rHu-IL-11) is a multifunctional cytokine with thrombopoietic activity and demonstrated clinical efficacy in treating chemotherapy-induced thrombocytopenia. rHu-IL-11 also exhibits anti-inflammatory activity and is currently in clinical trials for the treatment of several inflammatory diseases. As neutrophils are involved in both innate immunity and an acute inflammatory response, the effect of rHU-IL-11 on the function of human peripheral blood neutrophils in vitro was examined. rHu-IL-11 was not cytotoxic and did not induce superoxide anion production or the release of granular enzymes from resting neutrophils. Phagocytosis and chemotaxis were unaffected. rHu-IL-11 treatment did not block the response of neutrophils to stimulation. Pretreatment with rHu-IL-11 did not reduce production of IL-8 following activation with lipopolysaccharide (LPS) or zymosan A particles. Pretreatment with rHu-IL-11 did not affect the release of lysozyme and beta-glucuronidase in response to A23187 or PMA-stimulated production of superoxide anion. These results indicate that rHu-IL-11 does not directly modulate key functions of neutrophils in vitro.

Cells, Cultured↗
PubMed1998

Alveolar bone grafting: a review of 115 patients.

The results of alveolar bone grafting carried out at The Hospital for Sick Children, Great Ormond Street, London, UK, between January 1982 and January 1989 were assessed. Cancellous bone from the iliac crest was grafted to alveolar cleft defects in 115 patients (63 male and 52 female). Eighty-seven unilateral (58 left and 29 right) and 28 bilateral clefts were operated on. The mean age at the time of operation was 11.5 years, with a range of 8.08-18.75 years. The cleft canine had erupted prior to bone grafting in 58.4 per cent. At the time of this study the cleft had erupted in 96.35 per cent and was unerupted in 3.65 per cent of sites. Radiographs were taken at regular intervals and assessed according to previously reported criteria. Eighty-six per cent were clinically successful (Type I and II). In Type III 10.95 per cent had less than three-quarters of the normal interdental septal height and 2.18 per cent failed (Type IV). In addition, 3.6 per cent of sites showed cervical root resorption affecting the adjacent incisor and 1.4 per cent internal resorption of the cleft canine.

Adolescent↗
PubMed1998

Protective cytotoxic T lymphocyte responses against paramyxoviruses induced by epitope-based DNA vaccines: involvement of IFN-gamma.

Plasmid DNA vectors have been constructed with minigenes encoding a single cytotoxic T lymphocyte (CTL) epitope from either the M2 protein of respiratory syncytial virus (RSV) or from the nucleoprotein of measles virus (MV) with or without a signal sequence (also called secretory or leader sequence). Following intradermal immunization, plasmids in which the CTL epitopes were expressed in-frame with the signal sequence were more effective at inducing peptide- and virus-specific CTL responses than plasmids expressing CTL epitopes without the signal sequence. This immunization resulted in protection against MV-induced encephalitis and a significant reduction in viral load following RSV challenge. The reduction of viral load following RSV challenge was abrogated by prior injection with anti-IFN-gamma antibodies. These results highlight the ability of epitope-based DNA immunization to induce protective immune responses to well-defined epitopes and indicate the potential of this approach for the development of vaccines against infectious diseases.

Amino Acid Sequence↗
PubMed1998

Masking of irregular corneal topography with contact lenses.

PURPOSE: We examined the effectiveness of various types of contact lenses in masking irregular corneal topography using videokeratoscopy, residual aberrations, and measurement of visual acuity. METHODS: Thirteen subjects with differing degrees of keratoconus were recruited. Four types of soft lenses were used that varied in both thickness and water content, along with a rigid gas permeable (RGP) and a flexible gas permeable contact lens. RESULTS: RGP contact lenses provided the best visual acuity and the least residual aberrations. Flexible gas permeable lenses showed a reasonable masking of corneal distortion but did not provide the expected improvement in visual acuity. Soft contact lenses provided marginally better visual acuity than spectacle correction, but the level of residual aberrations was still high, even for relatively thick soft lenses (up to 0.2 mm). A significant correlation existed between the regularity of the front surface of the contact lenses on the eye and visual acuity in low illumination. CONCLUSIONS: Among the currently available contact lens materials, RGP lenses provide the best visual performance for subjects with keratoconus.

Adult↗
PubMed1998

Laboratory surveillance of hepatitis C virus infection in England and Wales: 1992 to 1996.

Screening assay for antibody to hepatitis C virus (HCV) became available late in 1990 and their use has subsequently become widespread. Laboratories in England and Wales reported 5232 confirmed HCV infections to the PHLS Communicable Disease Surveillance Centre (CDSC) between 1992 and 1996. Fifty-seven per cent (2976) of reports included risk factor information, 80% of which (2382) identified injecting drug use as the main route of transmission. Thirty-one per cent of reports (1640) included clinical information: 41% (665) were asymptomatic, 57% (938) had symptoms, signs, or biochemical abnormalities of hepatic origin, and 2.2% (37) had non-hepatic conditions. To enhance these data two additional surveys have been undertaken to collect data on all anti-HCV tests performed in public health laboratories. In 1993, a retrospective survey of people tested between 1990 and 1993 revealed that the prevalence of antibody was highest (222/331 [67%]) among injecting drug users and recipients of blood or blood products (189/548 [34%]) and lower among other groups. In a prospective survey of HCV tests performed in transfusion recipients in early 1995, the prevalence of antibody was higher in those transfused before 1985 (11/418 [2.6%]) than in those transfused after 1985 (14/1441 [1.0%]). Reports of confirmed infections are a useful method of monitoring hepatitis C infection but additional data on testing are needed to interpret trends overall and in specific risk groups.

Adolescent↗
PubMed1997

Dissociation of cytokine signals for proliferation and apoptosis.

Cytokines such as IL-2 or IL-3 prevent cell death through apoptosis, either by preventing apoptosis directly or by sensitizing cells to survival factors present in serum. We demonstrate herein that BAF-B03 cells transfected with the wild-type IL-2R beta-chain undergo apoptosis when stimulated with IL-2 or IL-3 in the absence of serum. IL-2 also induced apoptosis in normal IL-2-responsive human T cell blasts in the absence of serum, and furthermore, epidermal growth factor and fibroblast growth factor induced increased rates of apoptosis in fibroblasts in the absence of serum, suggesting that cytokine-induced apoptosis in the absence of serum survival factors might represent an important biologic phenomenon. In the presence or the absence of serum, IL-2 and IL-3 induced expression of both c-Myc and Bax. In contrast, optimal cytokine-induced expression of Bcl-2 requires serum. Constitutive expression of Bcl-2 prevented cytokine-induced apoptosis. Transferrin mimicked serum by inducing an increase in Bcl-2 expression levels and concurrently prevented apoptosis. These results suggest that the balance between cytokine- and serum-induced Bcl-2 expression and cytokine-induced Bax expression may determine whether a cell undergoes cytokine-induced apoptosis. In BAF/BO3 cells expressing a mutant IL-2Rbeta with a deletion of the acidic domain, IL-2 did not induce either Bax expression or apoptosis. This suggests that the acidic domain of the IL-2R beta-chain plays an essential role in regulating IL-2-mediated Bax expression and apoptosis. Cytokine-induced apoptosis and its counterbalance by survival factors present in serum may play an important role in the regulation of cellular homeostasis during pathophysiologic processes.

Animals↗