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Biomedical subjects

M Collins

Publications and source records attributed to M Collins.

At least 91 records · Page 5Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

A role for JNK/SAPK in proliferation, but not apoptosis, of IL-3-dependent cells.

Activation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) has been implicated in the induction of apoptosis in a variety of systems [1] [2] [3] [4] [5] [6] [7] [8]. BAF3 cells are pre-B cells that undergo apoptosis following IL-3 withdrawal or ceramide treatment [9] [10]. JNK/SAPK in BAF3 cells is stimulated by ceramide and also during cell proliferation in response to IL-3 [11], but its role in the apoptotic response is not clear. We have devised a method of selectively inhibiting JNK/SAPK activity using a dual-specificity threonine/tyrosine phosphatase, M3/6. Expression of this phosphatase in BAF3 cells prevented ceramide stimulation of JNK/SAPK activity but did not affect apoptosis following IL-3 withdrawal or ceramide treatment. IL-3-stimulated proliferation of BAF3 cells expressing the phosphatase was, however, inhibited. Hence JNK/SAPK activation is likely to be involved in the proliferative response of these cells but is not required for apoptosis. Selective ablation by dual-specificity phosphatases should be a general method for determining the functions of specific mitogen-activated kinase pathways.

Animals↗

CP-101,606, a potent neuroprotectant selective for forebrain neurons.

The neuroprotective activity of (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (CP-101,606), an N-methyl-D-aspartate (NMDA) receptor antagonist structurally similar to ((+/-)-(R*,S*)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-++ +piperidineethanol (ifenprodil), was investigated in neurons in primary culture. CP-101,606 potently and efficaciously protected hippocampal neurons from glutamate toxicity but was > 900-fold less effective for cerebellar granule neurons. The neuroprotective activity in the hippocampal neurons is mediated through a high affinity binding site distinct from the agonist and thienylcyclohexylpiperidine (TCP) binding sites of the NMDA receptor. Autoradiography indicates the CP-101,606 binding site is localized in forebrain, most notably in hippocampus and the outer layers of cortex. The functional selectivity for hippocampal neurons, forebrain localization of binding sites, and structural relation to ifenprodil suggest that CP-101,606 is an NMDA antagonist highly selective for NR2B subunit containing receptors.

Animals↗

Influence of hepatitis G virus infection on the severity of liver disease and response to interferon-alpha in patients with chronic hepatitis C.

BACKGROUND: Dual infection with hepatitis G virus (HGV) and hepatitis C virus (HCV) is common. The effect of HGV infection on chronic hepatitis C is not well known. OBJECTIVE: To assess the prevalence of HGV infection; the effect of HGV infection on the clinical, virologic and histologic features of patients with chronic hepatitis C treated with interferon-alpha; and the influence of HGV infection on response to interferon-alpha therapy. DESIGN: Retrospective study. SETTING: A university hospital in France. PATIENTS: 228 patients with chronic hepatitis C treated with interferon-alpha (3 million U or 5 million U subcutaneously 3 times a week for 3, 6, or 12 months). MEASUREMENTS: Before initiation of treatment, serum HGV RNA and serum HCV RNA were detected with branched-DNA assays and HCV genotype was determined with a line probe assay. Serum HGV RNA and serum HCV RNA were detected by polymerase chain reaction at the end of treatment and 6 months after treatment. RESULTS: Infection with HGV was detected in 21% of patients and 32% of intravenous drug users. The median serum HGV RNA level was 33 x 10(6) genome equivalents/mL. Infection with HGV was more frequently found in men with a history of intravenous drug use and was associated with HCV genotype 3a (P = 0.02) independent of the source of infection. Serum HCV RNA levels, liver histologic findings, and response to interferon-alpha therapy did not differ between patients with and those without HGV infection. The loss of serum HGV RNA was not correlated with the biochemical response contrarily to the loss of serum HCV RNA. CONCLUSIONS: Infection with HGV occurred frequently in this sample of patients with chronic hepatitis C, especially in patients infected with HCV genotype 3a. The level of HGV viremia was high relative to the level of HCV viremia. Infection with HGV did not influence the severity of liver disease or response to interferon-alpha therapy.

Adult↗

Regulation of the human alpha 2(1) procollagen gene by sequences adjacent to the CCAAT box.

The human, rat, mouse and chicken alpha 2(1) procollagen promoters analysed to date all contain an inverted CCAAT box at -80. In this study we have examined the binding of nuclear proteins to the proximal promotor of the human alpha 2(1) procollagen gene, where an inverted CCAAT box is flanked by a downstream GGAGG sequence and its inverted counterpart (CCTCC) on the upstream end. Each of the GGAGG sequences is separated from the inverted CCAAT box by a single pyrimidine nucleotide (5'-CCTCCCATTGGTGGAGGCCCTTTT-3'). Electrophoretic mobility-shift assays (EMSAs) revealed that two distinct DNA-protein complexes formed on this DNA sequence. Methylation interference analysis and in vitro mutagenesis studies revealed that the integrity of the sequence 5'-CCTCCCATTGG-3' (the GGAGG/CCAAT-binding element or G/CBE) was important for the binding of the CCAAT-binding factor (CBF) (complex I). Competition studies showed that complex formation on the human G/CBE could be competed by mouse CBE and nuclear factor-Y (NF-Y) oligonucleotides, suggesting that mouse CBE and human G/CBE-binding proteins belong to the same family of CCAAT box binding proteins. Furthermore, antibodies to mouse CBF specifically supershifted the G/CBE complex (complex I) in EMSAs. The downstream GGAGG and 3'-flanking sequences (5'-GGAGGCCCTTTT-3') or collagen modulating element (CME), however, were important for the formation of a novel DNA protein complex (complex III). The formation of this complex was not competed out by CBE or NF-Y oligonucleotides, nor was DNA-protein complex formation affected by the anti-CBF antibody. Functional analysis of G/CBE and CME elements subjected to mutagenesis, using promoter-chloroamphenicol acetyl transferase constructs in transient transfection assays, showed that both these elements were essential for activity of the human promoter. These experiments identified a novel regulatory element in the human alpha 2(1) procollagen gene which is not present in the rodent gene.

Cell Line, Transformed↗

Hepatitis C and G co-infection: response to interferon therapy and quantitative changes in serum HGV-RNA.

Hepatitis G virus (HGV), a positive sense RNA virus, is distantly related to hepatitis C virus (HCV): its genetic organization and identity are consistent with the Flaviviridae family. Coinfection with HGV occurs in 10% to 20% of HCV-infected subjects. These similarities raise two theoretical questions. First, could HGV coinfection play any role in the response of HCV to antiviral therapy and second, would this coinfected population have changes in serum HGV-RNA induced by interferon. To address these questions, 98 patients with documented chronic HCV underwent interferon therapy (3 million units three times a week) for 6 months. Response to therapy was categorized using standard biochemical criteria. Changes in HGV-RNA levels were evaluated before, during, and after interferon therapy by a quantitative branched DNA amplification research-based assay. Eleven of 98 (11%) patients with HCV infection had detectable serum HGV-RNA. There was no difference between the groups (HGV+ vs. HGV-) when baseline alanine aminotransferase (ALT) values, HCV-RNA levels, HCV genotype, histological severity, or other demographic features were analyzed. Interferon response was similar in both groups and HGV was not associated with outcome following therapy. Antiviral therapy appeared to induce a reduction in HGV-RNA load in five of nine patients coinfected with HCV serially tested. In two patients, the fall in serum HGV-RNA correlated with biochemical response, independent of changes in HCV-RNA. These observations indicate that a larger study of an HGV population is required to more clearly define the relationship between HCV and HGV coinfection and their response to antiviral therapy.

Aged↗

The effect of tramadol on dento-alveolar surgical pain.

The aim of the study was to assess the analgesic effect of tramadol in the relief of pain after dentoalveolar operations that involve the removal of bone and suturing. Four-hundred and fifty-two patients over the age of 18 years who were to undergo removal of impacted teeth (n = 362), removal of root (n = 79), or alveolectomy, enucleation of cysts, or removal of soft tissue (n = 11) under local anesthesia were studied. Patients were randomly allocated to receive tramadol 100 mg or 50 mg four times daily, or 50 mg twice daily, or placebo. Median pain scores on the day of operation in the three tramadol groups were similar (2 in each group, ranges 1-5, 1-4.8, and 1-5 respectively) and were all significantly lower than that in the placebo group (2.3 range 1-4.2). The median number of Paracetamol tablets taken by patients in the three tramadol groups was 2 (ranges 0-8, 0-12 and 0-8 respectively), and were all significantly less than in the placebo group (4, range 0-12). More patients given tramadol reported complete pain relief than the placebo group. The advantages of tramadol continued over the next 2 days. There were no serious or unexpected adverse effects. It is concluded that tramadol is an effective analgesic after dentoalveolar operations.

Acetaminophen↗

A computer-interfaced vertometer system for contact lenses.

BACKGROUND: The conventional vertometer (lensometer) is difficult to use for accurate measurement of contact lenses whose back vertex power (BVP) varies across the optic zone. BVPs of multifocal rigid and soft contact lenses have previously been measured using a conventional vertometer incorporating the Scheiner principle, which makes use of two light paths equidistant from the center of the lens. METHODS: We have developed a computer-based vertometer system based on the Scheiner principle which can be used to produce a profile of BVPs across rigid and soft contact lenses. A computer interface to the vertometer allows rapid acquisition of readings and software-based ray tracing derives in-air dioptric power readings across the optic zone at specific ray heights. RESULTS: Results are presented for soft and rigid, and spherical and aspheric surface contact lenses. CONCLUSIONS: The system improves the measurement resolution of a standard vertometer and shows an acceptable level of precision and accuracy for most applications.

Contact Lenses↗

What do children aged 5 to 11 years old know about the sun and skin cancer? The practical difficulties of international collaborative research when analysis of language is involved.

The objective of this study was to determine the perceptions of primary school children about sun exposure and skin cancer, and the language they use about these issues, as a basis for the design of health promotional materials. In all, 2857 children in five European countries took part in the study and were compared with 641 Australian children participating in a similar study, since the latter have been exposed to more intensive health education about the sun. The 'draw and write' technique was used. In Europe the level of awareness about the risks of excessive sun exposure and the need to protect the skin was considerably lower than in Australia, although there was some variation within northern Europe. Amongst the European children acknowledging a need to protect the skin, the principal means of protection quoted was the use of suncreams, with inadequate awareness of the value of clothing, hats and shade. European children expressed greater approval of suntans than did the Australian children. Some methodological problems were encountered as a result of nuances in the languages involved, emphasizing difficulties in international research of this type.

Age Factors↗

Subclinical hallucinations and delusions in nonpsychotic adolescents.

A number of studies have suggested that clinical populations of adolescents may report hallucinations and/or delusions without meeting criteria for a psychotic disorder. The purpose of this study was to provide information about the prevalence and symptom correlates of these subclinical hallucinations and delusions that occur in a nonpsychotic population of adolescents. Thirty-eight adolescents from a residential program and day treatment center were assessed with respect to hallucinatory experiences, ideas of reference, paranoid ideation, dissociative experiences, depressive symptomatology, and schizotypal cognitions. Results of this study indicated that 33% of the participants reported having experienced auditory hallucinations, and 24% reported having had delusional ideas. In addition, the results suggest that subclinical auditory hallucinations may have an especially strong relation with dissociative processes, whereas subclinical delusions appeared to be most strongly correlated with schizotypal thought processes. The results of this study begin to clarify the phenomenon of hallucinatory and delusional experiences in a nonpsychotic population.

Adolescent↗

bFGF induces BCK promoter-driven expression in muscle via increased binding of a nuclear protein.

Changes in gene expression occurring during skeletal muscle differentiation are exemplified by downregulation of brain creatine kinase (BCK) and induction of muscle creatine kinase (MCK). Although both are transcriptionally regulated, there appears to be no transcription factor-element overlap, suggesting that their coordinate expression results from culture medium-related influences. Basic fibroblast growth factor (bFGF) prevents myogenesis and represses MCK expression by inhibiting transcriptional activation. It was hypothesized that bFGF similarly influenced BCK by inducing its expression. Accordingly, BCK promoter constructs were transiently transfected into C2C12 cells and, after a switch to differentiation medium, were treated with bFGF, bFGF plus herbimycin, adenosine 3',5'-cyclic monophosphate (cAMP), or phorbol 12-myristate 13-acetate (PMA). Analyses demonstrated that bFGF responsiveness was contained within a 33-base pair element. Electromobility shift assays showed that bFGF induction increased the abundance of the nuclear factor binding the element. Both effects were prevented by herbimycin. Neither cAMP nor PMA specifically induced the construct containing the bFGF-responsive element. The induced factor required phosphorylation to bind, implying that bFGF-mediated increases in binding may be due to transcription factor phosphorylation.

Animals↗