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Biomedical subjects

S J Bell

Publications and source records attributed to S J Bell.

At least 37 records · Page 2Linked to original sources
PubMed1999

Severity of liver disease in hepatitis C infection contracted through injecting drug use.

BACKGROUND: Injecting drug use (IDU) is currently the most common route of hepatitis C virus (HCV) transmission in Australia and many other Western countries. Most reports on the natural history of HCV have examined populations that included patients from all risk groups, but it is possible that this increasingly important subgroup is different. AIMS: To assess the severity of liver disease in individuals who acquired HCV through IDU. METHODS: Three hundred and forty-six patients with confirmed HCV infection and a history of IDU, who had had a liver biopsy performed were recruited from a liver clinic. Demographic data, liver function tests and hepatitis B serology were obtained on all patients. A detailed drug use history and HCV viral studies were also available in a subgroup of 142 patients. RESULTS: Mean age of the group was 34 years and 73% were male. Mean duration of HCV infection was 14.6 years. Forty one per cent were infected with genotype 3a, 19% - 1a, 17% - 1 (nonsubtypable), 14% - 1b and 4% - 2b. Cirrhosis was present in 12% of patients. Patients with cirrhosis (38 years) were older than those with chronic hepatitis (34 years; p=0.0003) and had a longer duration of infection (17.2 vs 14.3 years; p=0.003). On multivariate analysis, however, patient age was the only factor independently associated with cirrhosis (odds ratio 4.2; 95% confidence interval 1.4-12.6). CONCLUSION: While cirrhosis is less common in this group than in other HCV infected populations, its prevalence may increase as these patients are followed over a longer period of time.

Adult↗
PubMed1998

Correlation of chi orientation with transcription indicates a fundamental relationship between recombination and transcription.

Cross-over hot-spot instigator (Chi) sequences (5'-GCTGGTGG-3') are abundant, strand-specific, sequences, which locally increase recombination in Escherichia coli. Located within G-rich 'recombination islands', Chi orientations correlate with the orientations both of DNA replication and of transcription. Consistent with evidence from eukaryotic systems for a fundamental relationship between recombination and transcription, we find for E. coli Chi sequences, and for Haemophilus influenzae Chi-like sequences, that orientations correlate better with transcription than with replication. Complying with Szybalski's transcription direction rule, open reading frames in these prokaryotes have purine-rich mRNA-synonymous DNA strands. Hence, the G-richness of 'recombination islands' may reflect their correspondence with 'transcriptional islands' (genes). Comparison of a natural with the corresponding shuffled sequence, indicates a base order-dependent island unit of approx. 1kb. 1998 Elsevier Science B.V.

Base Composition↗
PubMed1997

The new dietary fats in health and disease.

Lipids are an integral part of the routine diet of patients and the general public. In this article, the physiologic properties of various dietary lipids are reviewed, beginning with those most commonly consumed-the long-chain triglycerides (LCTs) and extending to those with special purposes: the short- and medium-chain triglycerides. The nutritional dietary management of patients typically includes physical mixtures of lipids. Recently, structured triglycerides (STs), which combine advantages from conventional fats with those of special purposes, have become available. STs are currently developed by interesterifying a mixture of conventional fats and oils, usually with medium-chain triglycerides, to achieve a specific fatty acid profile. This results in a triglyceride containing combinations of short-, medium-, and long-chain fatty acids on a single glycerol backbone. They have unique chemical, physical, or physiologic properties that are not observed by simply blending mixtures of the starting fats and oils. A number of STs are under intense laboratory and clinical investigation in models of cancer, burns, and immune dysfunction. Much interest in the fatty acids resides in the sn-2 position on the glycerol molecule. This is because the fatty acid in the sn-2 position of triglycerides is preferentially absorbed as the 2-monoglyceride and serves as the template for reesterification by intestinal cells to re-form triglycerides. The sn-2 fatty acids are also preferentially preserved as components of chylomicrons and very-low-density lipoprotein particles for ultimate incorporation in tissue membranes. Technology is evolving to create STs with a selected fatty acid in this sn-2 position. For instance, incorporating linoleic, arachidonic, or eicosapentaenoic acid at the sn-2 position is being evaluated for the specific objective of modulating serum cholesterol concentrations and essential fatty acid absorption (a review of this work is included).

Absorption↗
PubMed1997

Oral nutrition for the patient with HIV infection.

In the era of highly active antiretroviral therapy, it is unclear what percentage of patients with HIV infection will develop nutritional issues, including weight loss, diarrheal illness and anorexia. The purpose of this article is to discuss nutritional concerns that can occur with HIV infection and potential treatment strategies. We have included 3 case studies identifying these issues and a nutritional assessment guideline. Nutrition interventions, exercise recommendations, and other alternative strategies to combat HIV associated weight loss is discussed.

Adult↗
PubMed1996

A role for Th2 T-memory cells in early airway obstruction.

The role of T-cell memory in late-phase allergic lung inflammation is not well defined. To evaluate the role of systemic T-cell memory in allergic late-phase lung inflammation, BALB/c mice were injected intraperitoneally with ovalbumin (OVA) or ragweed (RW) allergens (Test I and Test II groups) or saline (control groups C I and C IV) and then challenged intratracheally with the allergen. Late-phase allergic lung inflammation was defined by: (i) recruitment of eosinophils to airways, (ii) IL-5 mRNA upregulation in BAL fluid cells, and (iii) detection of a Th2 cell cytokine profile in BAL fluids. The number of eosinophils recruited in allergic mice following intratracheal challenge with allergen was at least 300-fold higher P < or = 0.01) in mice with allergen-specific T-memory cells in BAL fluid (Test I and Test II) than in control mice without allergen-specific T-memory cells (C I and C IV). Further, the number of eosinophils recruited in Test I and II correlated with the magnitude of in vitro T-cell memory responses (r = 0.93, P < or = 0.04). Moreover, IL-5 mRNA upregulation in BAL cells and Th2 cytokine production in BAL fluids were observed only in Test I and Test II, and not in any of the control groups. Further, results from pulmonary function tests performed on the same allergic animals indicated that only animals from Test I and Test II groups had impaired lung function after allergen challenge. Taken together, these data strongly suggest that allergen-specific Th2-type T-cell memory is required for the development of allergic asthma. That is, without T-cell memory responses, no eosinophil recruitment and release of EPO (which is known to induce bronchoconstriction) occurred in the airways, and no Th2 cytokine profile was detected in the BAL fluid. Furthermore, if the Th2 cytokine profile was absent, then pulmonary functions remained normal.

Allergens↗
PubMed1996

High-energy, high-protein, oral, liquid, nutrition supplementation in patients with HIV infection: effect on weight status in relation to incidence of secondary infection.

OBJECTIVE: to evaluate the use of high-energy, high-protein, oral, liquid, nutrition supplementation and nutrition counseling on the weight status of patients infected with the human immunodeficiency virus (HIV) with and without secondary infections. DESIGN: Prospective, descriptive, intervention trial. Follow-up clinic visits were scheduled every 1 to 3 weeks for at least 6 weeks to monitor weight, gastrointestinal symptoms, number of supplements consumed, and incidence of secondary infections. SUBJECTS/SETTING: Community-based, HIV-infected patients, with and without an acquired immunodeficiency syndrome (AIDS) defining illness, who were receiving outpatient medical care at Deaconess Hospital. Twenty-two patients enrolled; however, 4 dropped out and 1 died, so 17 were eligible for evaluation. INTERVENTION: Dietary counseling consisted of recommendations to consume a high-protein diet (1.5 g/kg ideal body weight); select foods that minimize gastrointestinal complications; and take at least one high-energy, high-protein, oral, liquid, nutrition supplement daily. MAIN OUTCOME MEASURES: Energy intake from the supplements and weight change over time in relation to whether a secondary infection occurred. STATISTICAL ANALYSIS: Means, standard deviations, and frequency. RESULTS: At the time of entry to the study, the patients with preexisting weight loss (16 of 17) were 14+/-8% below their usual body weight. On average, patients consumed 11+/-4 supplements per week for 6+/-3 weeks. The majority (12 of 17) were able to gain or maintain weight. Overall weight change was 1.1+/-2.2 kg. Only 5 of 17 patients lost weight, 4 of whom developed a secondary infection during the study (ie, after enrollment in the study). All of those who developed a secondary infection were classified as having AIDS and had lower mean CD4 counts at baseline than those who did not develop a secondary infection. Although those who developed a secondary infection had a higher incidence of weight loss, their consumption of oral supplements per week was greater than that of those without a secondary infection. APPLICATIONS/CONCLUSIONS: In patients with HIV infection and in the early stages of AIDS without a secondary infection, weight gain and/or maintenance was achievable with a high-energy, high-protein, oral, liquid, nutrition supplement in conjunction with nutrition counseling. The majority of the patients who developed a secondary infection, however, lost weight despite the use of supplements and counseling. Use of a high-energy, high-protein, oral, liquid, nutrition supplement, with intact nutrients, should be the first-line nutrition treatment for malnourished, HIV-infected patients without secondary infections.

AIDS-Related Opportunistic Infections↗
PubMed1996

Classical Kaposi's: a rare cause of gastrointestinal haemorrhage.

Classical Kaposi's sarcoma (KS) is an indolent neoplasm involving mucocutaneous sites predominantly in elderly Mediterranean or Jewish persons. Whilst gastrointestinal involvement is common, it is usually asymptomatic. This case report presents a case of massive gastrointestinal haemorrhage in a patient with stable cutaneous disease and outlines options for the investigation and management of this rare complication.

Aged↗
PubMed1995

Staphylococcal enterotoxin B modulates V beta 8+ TcR-associated T-cell memory against conventional antigen.

Primary in vivo challenge with the superantigen staphylococcal enterotoxin B (SEB) induces polyclonal proliferation of an unusually large proportion of circulating T-cells that bear the V beta 8-T-cell receptor (TcR) domain. Early and vigorous proliferation of V beta 8+ T-cells precedes their selective deletion, leaving the host unresponsive upon rechallenge with the native immunogen SEB. Nonetheless, this induction of anergy is incompletely understood. Recently we demonstrated that more cells than just V beta 8+ T-cells undergo clonal proliferation after challenge with SEB (Cell. Immunol. 154, 440, 1994). These findings suggested that non-V beta 8+ T-cells may have a role in the induction of superantigen-induced anergy. To further investigate this, we enumerated CD4+ and CD8+ T-cells in lymph nodes and spleens from Balb/c mice at various times after primary and secondary challenge with either a high or a low dose of SEB. Using these kinetic data we investigated whether challenge with SEB would modulate antigen-specific V beta 8-associated T-memory responses. To this end, the V beta 8+ T-cell-associated responses induced by SEB were compared with the V beta 8+ TcR-associated memory responses induced by the nominal antigen sperm whale myoglobin (SWM). Results indicated that challenge of SWM-primed mice with SEB abrogated the V beta 8-associated SWM-specific T-cell memory for an extended but transient period of time. Moreover, prechallenge with SEB blocked the establishment of de novo V beta + T-cell-mediated immunity. These findings suggest that administration of low and controlled doses of microbial superantigen could provide long-term suppression of antigen-specific cell-mediated immunity.

Animals↗
PubMed1995

Determination of combined benzidine in FD&C Yellow No. 6 (Sunset Yellow FCF).

Samples from 67 manufactured lots of FD&C Yellow No. 6 (Sunset Yellow FCF; Colour Index No. 15985) were analysed for combined benzidine. These samples were selected from those submitted to the US Food and Drug Administration for certification between October 1991 and December 1992 by 13 dye distributors. Dithionite was used to reduce any combined benzidine present in the form of azo or disazo dyes to free benzidine. This reduction was followed by extraction, diazotization and coupling with 2-naphthol-3,6-disulfonic acid disodium salt (R salt). The total benzidine was quantified as benzidine-R salt disazo dye by HPLC with detection at 540 nm and a quantification limit of 10 ng benzidine/g FD&C Yellow No. 6. Of the 67 samples analysed, 34 were found to contain more than 10 ng combined benzidine/g. Of these, 30 samples were from one manufacturing company, including three of its subsidaries. The level of combined benzidine found ranged from 11 to 104 ng/g, except for one sample containing 941 ng/g.

Azo Compounds↗
PubMed1995

Generic enteral formulas: a new idea for the 1990s.

Generic equivalent enteral formulas are now commercially available. The purpose of this article is threefold: (1) to define generic equivalents and compare both their nutritional and monetary differences with brand name products, (2) to provide the clinician with factors to consider when evaluating generic formulas--the source and distribution of macronutrients and micronutrients, and patient tolerance, nutritional status and outcome--and (3) to provide information on how to incorporate generic enteral formulas onto an institution's enteral formulary. In today's environment of diminishing health care budgets, generic enteral formulas can play a role in cost containment without sacrificing quality nutritional care.

Aged↗
PubMed1994

Early activation and cell trafficking induced by staphylococcal enterotoxin B: effects of high- versus low-dose challenge on induction of anergy.

The in vivo challenge with exogenous superantigen, staphylococcal enterotoxin B (SEB), selectively induces vigorous polyclonal proliferation of T cells bearing the V beta 8+ TcR domain, whereafter the responsive cells become anergic. We used kinetic analyses to compare the effects of primary (1 degree) and secondary (2 degrees) challenge with a high and a low dose of SEB and the conventional antigen, sperm whale myoglobin, to determine the differential effects of in vivo challenge with a superantigen compared with a conventional antigen. We demonstrate that SEB induces very early activation-associated intralymphatic proliferation and trafficking of more T cells than can be accounted for by V beta 8+ T cells alone. Overall, this study indicates that challenge with SEB causes an apparent loss of CD4+ T-helper cell function and provides an essential foundation for the understanding of the mechanisms of peripheral tolerance induction and T cell "memory."

Animals↗
PubMed1994

Experience with enteral nutrition in a hospital population of acutely ill patients.

Enteral feeding has unique metabolic and immune advantages. This article describes the successful use of enteral nutrition, alone or in combination with parenteral feeding, in a tertiary-care hospital. Study participants were 89 patients who received enteral feeding during a 6-month period. These critically ill patients (ranging in age from 55 to 71 years) had severity of illness levels of 7 to 25 according to the Acute Physiologic and Chronic Health Evaluation (APACHE II) system and lengths of hospital stay from 27 to 73 days. Mortality was as high as 50% in patients with liver disease (nonmalignant), 35% in patients with cardiothoracic and vascular diseases, and 17% in patients with cancer and other diseases. Despite the severity of illness, patients met their energy and protein intake goals through enteral or combined feeding with total parenteral nutrition. Serial weights (ie, obtained weekly) and serum albumin concentrations did not improve during hospitalization. Complications related to enteral feeding were minimal (< 17% incidence). Differences were noted between survivors and nonsurvivors: nonsurvivors had lower serum albumin concentrations at the time of admission, had longer hospitalizations, and required total parenteral nutrition for more days than the survivors. Nonetheless, even with extremely sick patients, provision of enteral nutrition can be successful using the administration techniques we describe. Enteral nutrition could best be provided by beginning at a slow rate (10 c3/hour), inserting the feeding tube past the pylorus, and feeding according to sensible energy goals (25 kcal/kg of body weight), and using elemental then polymeric formulas.

Acute Disease↗
PubMed1993

Determination of combined benzidine in FD & C yellow no. 5 (tartrazine), using a highly sensitive analytical method.

53 samples of FD & C Yellow No. 5 (tartrazine; Colour Index No. 19140) were examined for combined benzidine. These samples, which represent separate lots from 12 dye distributors, were submitted to the US FDA for certification between 28 February 1990 and 27 June 1991. A method was developed to reduce the dye matrix with dithionite so that combined benzidine present in the form of azo or disazo dyes would be converted to free benzidine. Reduction was followed by extraction, diazotization and coupling with pyrazolone T, and the total benzidine present was quantitated as benzidine-pyrazolone T disazo dye (BZPT) by HPLC with detection at 500 nm. The limit of quantitation for benzidine in FD & C Yellow No. 5 by this method is 5 ng/g. 25 samples of FD & C Yellow No. 5 were found to contain 7-83 ng/g of combined benzidine that was released by dithionite reduction. 23 of these samples were from the same manufacturer. The identify of the BZPT from two FD & C Yellow No. 5 samples was confirmed by spectral analysis using HPLC with a photodiode array detector.

Benzidines↗
PubMed1993

Nutrition support and the human immunodeficiency virus (HIV).

Nutritional support of patients with HIV or acquired immune deficiency syndrome (AIDS) has many similarities to other disease states in that the same nutritional products and techniques are used. Some patients with HIV, and many with AIDS without secondary infection, experience a metabolic milieu similar to patients with cancer cachexia. In providing dietary counselling to the HIV patient, we encounter many of the obstacles that must be overcome to improve nutrition in cancer: anorexia, gastrointestinal discomfort, lethargy, and poor nutrient utilization, which limit the ability for nutritional repletion. When a secondary infection is superimposed on HIV, patients resemble more highly catabolic trauma patients or patients in the intensive care unit (ICU), where, despite aggressive efforts to feed, there is usually a net nitrogen wasting leading to the more rapid development of cachexia. However, even in this setting, feeding will limit substantially net catabolism when compared to total starvation. Because the nutritional needs of HIV patients vary greatly, individual strategies have to be designed as the patient moves through the stages of disease. Patients are generally able to consume adequate nutrition either as regular food or dietary supplements during the latency period of viral replication. Once secondary infections become prevalent, artificial diets administered by tube or by vein may be required during the period of active secondary infections, with dietary supplements often helpful during more quiescent periods. Patients with HIV are among the most challenging for clinicians providing nutritional support. Knowledge from treatment of patients with other diseases may be useful, but more data must be gathered on the unique aspects of aetiology and treatment of the anorexia, malabsorption, and ultimate wasting associated with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Augmentation of HIV-specific lymphoproliferation in HIV-infected individuals by TraT: a novel T-cell immunopotentiating agent.

OBJECTIVE: To evaluate the potential of TraT to restore HIV-specific cell-mediated immunity. DESIGN: CD4+ T cell-associated antiviral and recall antigen-specific lymphoproliferative responses are generally impaired or absent in HIV-infected individuals. METHODS: Using peripheral blood mononuclear cells (PBMC) from a group of asymptomatic and symptomatic HIV-infected individuals, we compared the immunomodulatory effects of exogenous interleukin-2 (IL-2) with the effects elicited by the bacterial integral membrane protein, TraT. RESULTS: Exogenous IL-2 enhanced lymphoproliferation induced by an immunodominant synthetic HIV gp41 analogue, gp41[8] (amino acids 593-604), in four out of 10 asymptomatics and six out of 19 symptomatics. In contrast, TraT acted synergistically with gp41[8] to augment HIV-specific proliferation with higher frequency and greater magnitude than exogenous IL-2. Moreover, this TraT-mediated enhancement of HIV-specific lymphoproliferation occurred in the majority of HIV-infected individuals, irrespective of CD4+ T-cell count in peripheral blood or disease status, and thus appears not to be major histocompatibility complex-restricted. TraT also augmented lymphoproliferation induced by well-known recall antigens and other less immunodominant HIV analogues. CONCLUSIONS: These findings suggest that TraT, in combination with HIV-derived peptides, could be used to maintain or restore cell-mediated immune functions of HIV-infected individuals, as well as cellular immune functions in individuals suffering from other immunodeficiency disorders.

Adjuvants, Immunologic↗
PubMed1992

CD8+ T-cells from HIV-infected patients can either augment or abrogate HIV-specific lymphoproliferation.

Despite the presence of activated CD8+ T-cells that have been identified in infected individuals, these cells do not overcome natural HIV infection. To understand this better, we analyzed the CD8+ cell-dependent HIV-specific lymphoproliferation that occurs after HIV infection. Our study group of 36 individuals included 11 asymptomatic and 16 symptomatic patients (12 ARC and 4 AIDS), as well as HIV-seronegative controls. After CD8+ cell depletion of PBMC cultures, the remaining cells were tested for proliferation during culture with a well-defined and immunodominant gp41-derived HIV analog, gp41(8). After CD8+ cell depletion, three functional outcomes, which differed in accordance with the disease status of the individual, were consistently recorded, namely (i) an "abrogation effect," (ii) an "augmentation effect," or (iii) "no effect." First, removal of CD8+ cells from PBMC cultures abrogated gp41(8)-specific lymphoproliferation in gp41(8)-specific responders. Paradoxically, in other patients, including 5 symptomatics, the same inhibition of CD8+ cell function caused significant augmentation of gp41(8)-specific lymphoproliferation. These results suggest that the subpopulations of CD8+ T-cells that predominate at different stages of HIV-induced disease have different functional properties, including the ability to modulate HIV-specific cell-mediated immunity.

CD8 Antigens↗
PubMed1992

Heterogeneous effects of exogenous IL-2 on HIV-specific cell-mediated immunity (CMI).

A characteristic feature associated with HIV-1 infection of the human host is a chronic decline in circulating CD4+ T helper/inducer cell numbers. Impaired cell-mediated immune functions usually occur in parallel with the decline in CD4+ T cells. Activated CD4+ T helper cells are a major source of endogenous IL-2 which is required for the immunoregulation of both antigen-specific B cells and CD8+ T cells. HIV-specific T cell proliferative responses are said to be weak and inconsistent, even during the asymptomatic phase of disease. We thus wished to determine how exogenous IL-2 affected HIV-specific T cell proliferation at different stages of the disease. Our cohort of 81 included both asymptomatic and symptomatic HIV-infected patients as well as uninfected normal donors. Proliferative responses of peripheral blood mononuclear cells (PBMC) that were elicited during culture with an immunodominant gp41-derived synthetic peptide, gp41[8], and which were known to be CD8+ cell-associated in asymptomatics only, were used to analyse the effects of exogenous IL-2. IL-2 had three main effects on HIV-specific proliferation, namely (i) an additive effect, (ii) a synergistic effect, and (iii) an induced effect. More specifically, low dose exogenous IL-2 frequently augmented lymphoproliferation in both asymptomatic and symptomatic gp41[8] responders. In most symptomatics, however, who were predominantly gp41[8] non-responders, exogenous IL-2 induced lymphoproliferation. Flow cytometric analyses using dual immunofluorescence were used to analyse the T cell subset distribution of proliferating PBMC cultures. During culture with gp41[8], both CD4+ and CD8+ T cell numbers increased. However, after the addition of exogenous IL-2 to gp41[8]-containing cultures, CD8+ cell-associated lymphoproliferative responses were preferentially augmented. These results suggest that in symptomatics there is an inadequate supply of endogenous IL-2 to help maintain the strong and effective CD8+ cell-associated anti-viral immunity, and an exogenous supply of IL-2 may be required.

Flow Cytometry↗