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Biomedical subjects

G Hall

Publications and source records attributed to G Hall.

At least 73 records · Page 4Linked to original sources

The role of mediated conditioning in acquired equivalence.

In Experiment 1 rats received initial training in which delivery of a sucrose pellet was signalled by an auditory cue. This cue was then paired with shock in a second phase of training. In a test the rats showed an unwillingness to perform an instrumental response that yielded the sucrose pellet. This was interpreted as indicating that the associatively activated representation of the pellet had acquired aversive properties during the shock-reinforced stage of training. Experiment 2 replicated this mediated conditioning effect making use of a Phase 1 training procedure, modelled on that used by Honey and Hall (1989) to demonstrate acquired equivalence of cues, in which two auditory cues were each used to signal sucrose pellets. A further test revealed that this training resulted in enhanced generalization between these two cues. It was argued that this effect is mediated by the conditioned aversive properties of the common associate of the two auditory cues.

Animals↗

The effect of route of immunization on mucosal immunity and protection.

In macaques, the route of immunization has a profound effect on the immune response. Augmenting rectal or vaginal immunization with oral or nasal immunization enhanced the secretory IgA, serum IgG, and T cell responses. However, targeted iliac lymph node (TILN) immunization with recombinant simian immunodeficiency virus (SIV) gp120 and p27 elicited the most consistent mucosal antibody responses in the rectum, vagina, urine, seminal fluid, and blood. Both mucosal and TILN immunization induced specific CD4+ T cell proliferative responses in the iliac lymph nodes, which drain these mucosal surfaces, and in the splenic and circulating T cells. Rectal mucosal challenge with cell-free SIV induced total protection in 4 of 7 macaques that were immunized by the TILN route, and, compared with unimmunized macaques or those immunized by the mucosal route (P<.001), it induced a >90% decrease in virus load in 3 of them. Protection from mucosal rectal infection with SIV was significantly associated with an increase in the CD8 suppressor factor (which was generated by the iliac lymph node), RANTES, and MIP-1beta (P<.01).

Animals↗

A randomized trial on effects of hormone therapy on ambulatory blood pressure and lipoprotein levels in women with coronary artery disease.

OBJECTIVE: To investigate 1-year effects of hormone replacement therapy (HRT) on ambulatory blood pressure (ABP) and lipoprotein levels in postmenopausal women with coronary artery disease (CAD). METHODS: Sixty patients at a mean age (+/- SD) of 59 +/- 7 years were randomized into three groups: conjugated equine oestrogens (CEE) 0.625 mg daily (n = 20), 50 microg 17beta-oestradiol transdermally (TTSE) per 24 h (n = 20) or placebo (n = 20) for 18 days, then combined with medroxyprogesterone acetate 5 mg for 10 days. Each cycle of 28 days was repeated for one year. RESULTS: Night-time systolic ABP had decreased by 9.6% (P= 0.0075) in 15 of 18 women in the CEE group and by 22% in 12 of 13 women (P = 0.0034) in the placebo group after 1 year. In the CEE group, a 4.6% rise in daytime systolic ABP (P< 0.05) and a 4.2% rise in night-time systolic ABP (P< 0.05) appeared from baseline to 6 months in 13 of 18 women. In the CEE group (14 women analysed), high-density lipoprotein levels showed a 15.8% increase (P= 0.0018) in 13 women, low-density lipoprotein levels a 15.2% decrease (P= 0.0129) in 12 women and total cholesterol levels a 7.5% decrease (P = 0.057) in 11 women after 1 year. Triglyceride levels showed no changes. In the TTSE group and in the placebo group, with 12 and 13 women analysed respectively, no significant changes appeared. CONCLUSIONS: One year of HRT in patients with CAD does not influence ABP. Oral HRT induces beneficial effects on lipoprotein levels.

Adult↗

Candida glabrata Fungemia. Clinical features of 139 patients.

Candida species are now the fourth leading cause of nosocomial bloodstream infection in hospitalized patients, and non-Candida albicans species now surpass Candida albicans. The clinical features of the most common non-Candida albicans species, Candida (Torulopsis) glabrata, have not been well studied. We retrospectively reviewed the clinical features of 139 patients with C. glabrata blood-stream infection over a period of 7 years. The mean age of patients was 62 years, and the most common admitting diagnoses were malignancy (28%) and coronary artery disease (18%). The most common identified portals of entry were abdominal (22%) and intravascular catheters (16%). At the time of fungemia, 63% of patients had fever, 45% had change in mental status, and 30% were in septic shock. Three of 50 patients examined by an ophthalmologist had chorioretinitis. The overall hospital mortality was 49%. Factors associated with increased mortality in a regression model were prior abdominal surgery (odds ratio [OR] = 2.8; 95% confidence interval [CI] = 1.2-6.3, p = 0.01), and an elevated creatinine (OR = 2.2; 95% CI = 1.0-4.7, p = 0.05). When early deaths (< or = 72 hours) were censored, amphotericin B treatment and total dose were associated with reduced mortality (OR = 0.2; 95% CI = 0.1-0.4, p < 0.001). Nosocomial C. glabrata fungemia is not just a disease of debilitated and neutropenic patients, but affects a wide variety of patients and is associated with a high mortality.

Aged↗

Antibody-secreting cells specific for simian immunodeficiency virus antigens in lymphoid and mucosal tissues of immunized macaques.

OBJECTIVES: To examine whether the route of immunization affects the induction of antibody-secreting cells (ASC) in the circulation of macaques. The distribution of ASC in the rectal mucosa and lymphoid tissues following challenge with simian immunodeficiency virus (SIV) was investigated. DESIGN: Macaques were immunized with recombinant SIV gp120 and p27 antigens by the targeted iliac lymph node (TILN) route of immunization or the nasal and rectal route, augmented by intramuscular immunization [naso-rectal intramuscular (NRI)]. The macaques were challenged with live SIV by the rectal route and ASC were assayed in the circulation before and after SIV challenge, and in the tissues removed at post-mortem. METHODS: ASC were examined in the circulation by Elispot assay. Mononuclear cells were prepared from peripheral blood, iliac and axillary lymph nodes and spleen. Rectal tissue was treated by enzyme digestion to elute mononuclear cells. RESULTS: TILN and NRI immunization induced circulating IgA and IgG ASC to both gp120 and p27. Following rectal challenge with SIV, TILN macaques were protected from infection whereas NRI route-immunized and unimmunized controls became infected. IgA ASC to p27 were increased significantly in the iliac lymph nodes of the TILN immunized macaques compared with unimmunized controls (P < 0.05). Only IgA ASC were found in the rectal mucosa of the immunized protected macaques but both IgA and IgG ASC were detected in the unimmunized infected macaques. Overall the number of IgG ASC specific for p27 was significantly higher in the infected NRI and control macaques than in the protected macaques (P < 0.02). A progressive increase in IgG but not IgA ASC was detected in the peripheral blood mononuclear cells of the unimmunized infected macaques. CONCLUSIONS: The results suggest that cells secreting IgA antibodies to p27 in the iliac lymph nodes of the TILN immunized macaques correlate significantly with protection from infection. The unimmunized infected macaques showed a progressive increase in IgG ASC in the peripheral blood after SIV challenge; this was found in the iliac and axillary lymph nodes and also in the spleen, suggesting that it is an immune response to the SIV infection.

Administration, Intranasal↗

Long-term effects of hormone replacement therapy on symptoms of angina pectoris, quality of life and compliance in women with coronary artery disease.

OBJECTIVE: The aim of the present study was to evaluate the effects of HRT on symptoms of angina pectoris, quality of life and factors of importance for compliance in women with ischemic heart disease. METHODS: Sixty postmenopausal women with coronary artery disease were randomized into three groups: one group received transdermal 17 beta-estradiol at a dose of 50 micrograms per 24 h alone for 18 days followed by 10 days of combined treatment with medroxyprogesterone acetate (MPA) 5 mg orally; the second group received placebo and the third group received conjugated estrogens orally for 18 days followed by a combined treatment with MPA for 10 days. Clinical evaluations were performed at baseline, after 3, 6 and 12 months. The investigations included gynecological history. occurrence of climacteric symptoms, quality of life evaluation, cardiac history and symptoms of angina pectoris. RESULTS: Forty-six women (77%) completed the study during 1 year. The following cardiac events occurred in the women who completed the study: one patient was hospitalized because of congestive heart failure (patch), two patients because of angina pectoris, one patient because of coronary bypass operation (CEE) and three patients underwent balloon dilatation (placebo), all three on CEE. Among the 14 women who discontinued, two patients had TIA (patch), one experienced palpitations (CEE) and one woman died from myocardial infarction (placebo). Overall improvement in mood and cognitive functions were reported in all three treatment groups. CONCLUSIONS: HRT does not seem to have negative effects on symptoms of angina pectoris and seems to increase quality of life in older women with coronary heart disease. It also seems safe from the cardiovascular point of view.

Aged↗

Comparison of E test and agar dilution methods for determining antibiotic susceptibilities of anaerobic bacteria and viridans streptococci isolated from blood.

The antimicrobial susceptibilities of 311 strains of anaerobic bacteria and 140 strains of aerobic bacteria, isolated from blood after dental extraction, were determined by the E test and compared with the results obtained by the agar dilution method on PDM-ASM 2 agar. E test MICs agreed within +/-1 dilution step to the agar dilution MICs in 93%, 52%, 90%, 94% of the tested anaerobes for penicillin V, cefaclor, clindamycin and erythromycin, respectively. For aerobic bacteria the agreement was > or = 90% for the antibiotics tested. The in vitro activities of penicillin V, clindamycin and erythromycin were higher than the activity of cefaclor against the majority of bacteria tested.

Journal Article↗

Illness-induced context aversion learning in rats with lesions of the dorsal hippocampus.

In 2 experiments, rats with electrolytic lesions of the dorsal hippocampus and sham-operated control subjects were given injections of lithium chloride after exposure to a distinctive context. This procedure establishes a context-illness association in intact subjects. In Experiment 1, the strength of the context aversion was assessed by measuring the subjects' willingness to consume a novel flavor in the context. It was found that lesioned subjects showed less suppression of consumption than controls. Experiment 2 tested the ability of the context to block subsequent flavor-aversion learning and revealed less effective blocking in lesioned rats. These results are consistent with the view that hippocampal lesions retard context conditioning; unlike previous work that has made use of conditioned freezing as the measure of context conditioning, the present results are not explicable in terms of lesion-induced changes in general activity.

Analysis of Variance↗

Comparison of the merits of measuring equine chorionic gonadotrophin (eCG) and blood and faecal concentrations of oestrone sulphate for determining the pregnancy status of miniature horses.

The relative merits of measuring blood concentrations of equine chorionic gonadotrophin (eCG, previously known as pregnant mare serum gonadotrophin (PMSG)), or oestrone sulphate (OS), or faecal OS concentrations for determining pregnancy status in miniature horses were investigated. Pregnant mares between 40 and 140 days after mating had serum eCG concentrations > 1 I.U. mL-1, with the highest concentrations occurring between days 50 and 120. However, eCG measurements were susceptible to returning a 'false positive' diagnosis of pregnancy. Plasma OS concentrations ranged from 0.1 to 3.6 ng mL-1 in non-pregnant mares, whereas pregnant mares beyond 100 days post-mating all had plasma OS concentrations > 30 ng mL-1. Faecal OS concentrations ranged from 4 to 89 ng g-1 in non-pregnant mares. For faecal samples collected from pregnant mares 150 days or more after mating, 97% of samples had OS concentrations > 85 ng g-1, the value 3 standard deviations above the mean non-pregnant value. None had values below 67 ng g-1, the value 2 standard deviations above the mean non-pregnant value. These results show that measurement of eCG is suitable for determining pregnancy status in miniature mares between 40 and 100 days post-mating. However, mares returning a 'pregnant' diagnosis should undergo a blood OS test 100 or more days after mating to eliminate the possibility of a 'false positive' diagnosis. Measuring blood OS is recommended as the method of choice for determining pregnancy status in miniature mares 100 or more days after mating. Faecal OS measurements provide a non-invasive alternative to blood OS testing from 150 days post-mating. However, the discrimination between 'pregnant' and 'non-pregnant' levels of OS is not as great in faeces as it is in blood.

Animals↗

Experimental campylobacter infection and diarrhoea in immunodeficient mice.

The responses of previously untested immunodeficient mouse strains to campylobacter infection are described. Three strains of adult immunodeficient mice (SCID-Beige, C.B-17-SCID-Beige and RAG-2) were inoculated intragastrically with Campylobacter jejuni NCTC 11168. All mice became heavily colonised, but none developed clinical signs of disease. Immunocompetent BALB/c mice inoculated similarly had much lower colonisation levels. The co-administration of iron dextran had no effect on colonisation levels nor the development of clinical signs of disease. In contrast, C.B-17-SCID-Beige mice, when inoculated with one of a series of 10 clinical isolates of C. jejuni, were more heavily colonised for extended periods (up to 5 months) and approximately 10-20% of the mice became ill with diarrhoea. C. jejuni was detected in mouse faeces throughout at levels of 10(7)-10(9) cfu/g. All mice killed whilst ill with diarrhoea displayed histopathological lesions typical of human campylobacteriosis. Severe pathology was limited to the large intestine and was suggestive of an acute, bacteria-induced inflammation. Although blood was detected in the diarrhoeal stools, no evidence of mucosal epithelial cell invasion was found by immunohistology. No pathology was detected in tissue sections from any of the animals that had not developed signs of disease following C. jejuni inoculation. These immunodeficient mouse strains are readily, and heavily, colonised as adults by C. jejuni. The diarrhoea, although sporadic, was reproducibly produced, and could provide the basis for pathogenicity studies.

Animals↗

Induction of tolerance via the respiratory mucosa.

Immunological tolerance is defined as a state of specific non-responsiveness to a particular antigen induced by previous exposure to that same antigen. The mucosal surfaces comprise the upper and lower respiratory tracts, the gastrointestinal tract and the urogenitary tract, and are a major site of antigenic challenge. The immune system associated with the mucosa has the extraordinary potential to discriminate between antigens that are harmless (e.g. inhaled and dietary antigens) and those that are associated with pathogens. Normally soluble proteins delivered through the mucosal surfaces do not elicit a strong systemic immune response but instead induce a transient local immune response that is replaced by long-term peripheral unresponsiveness this is termed mucosal tolerance. The phenomenon of oral tolerance is well established and considerable attention has focussed on defining the underlying mechanisms. However, only comparatively recently was the induction of tolerance via the respiratory mucosa described, and it is this form of mucosal tolerance which forms the basis of this review.

Humans↗

Using low-frequency oscillation to detect bronchodilator responsiveness in infants.

The potential of the low-frequency forced oscillation technique (FOT) to measure the response to inhaled salbutamol was studied in 13 infants with a history of recurrent wheeze and nine healthy infants. The input impedance of the respiratory system (Zrs) between 0.5 and 20 Hz was measured at a transrespiratory pressure of 20 cm H2O during a brief Hering-Breuer reflex-induced pause in breathing. Parameters representing the airway resistance (Raw) and inertance (law), and a constant-phase tissue damping (G) and elastance (H) were estimated from the Zrs spectra. Lung function was measured before and after the administration of 500 microg of salbutamol via a small-volume metal spacer. Six of these infants also received a placebo aerosol. A fall in Raw (13% for the entire group) occurred following treatment with salbutamol (p < 0.008) but not placebo. There was no significant difference in the response to salbutamol between the normal infants (7.65% +/- 5.49%) and those with recurrent wheeze (17.58% +/- 8.67%). On grouped data, the fall in G just failed to reach statistical significance (p = 0.05) after correcting the significance level for multiple tests. No significant change occurred in law or H. We conclude that the low-frequency FOT is a suitable methodology for studying bronchodilator responsiveness in infants.

Administration, Inhalation↗

Protective mucosal immunity elicited by targeted lymph node immunization with a subunit SIV envelope and core vaccine in macaques.

Prevention of sexually transmitted HIV infection was first investigated in non-human primates by mucosal immunization via the rectal, vaginal or male urethral route. This was compared with subcutaneous targeted iliac lymph node (TILN) and systemic intramuscular immunization in non-human primates. TILN immunization elicited the most consistent mucosal sIgA and IgG antibody response in the rectum, vagina, urine and seminal fluid, as well as in blood. Both mucosal and TILN immunization induced a specific CD4+ T cell proliferative response in the iliac lymph nodes which drain these mucosal surfaces, and in the splenic and circulating T cells. In the next experiment macaques were immunized by the TILN route with SIV gp120 and p27 in alum. Rectal mucosal challenge with SIVmac 32H J5 molecular clone (or cell-free virus) induced total protection in four out of seven macaques, compared with infection in 13 of 14 unimmunized macaques or immunized by other routes (p = 0.025). The remaining three macaques immunized by the TILN route showed either decrease in viral load (> 90%) or transient viraemia, indicating that all seven TILN immunized macaques showed total or partial protection of rectal transmission by SIV (p = 0.001). Protection was associated with significant increase in the iliac lymph nodes IgA antibody secreting cells to p27 (p < 0.02), CD8-suppressor factor inhibiting replication of SIV in CD4+ T cells (p < 0.01) and the chemokines RANTES and MIP-1 beta (p < 0.01). We suggest that administration of gp120 and p27 by the TILN route may elicit protective B and T cell immunity which can significantly prevent rectal transmission of SIV or HIV.

Animals↗