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Biomedical subjects

J Higgins

Publications and source records attributed to J Higgins.

At least 55 records · Page 3Linked to original sources
PubMed1994

Detection of antibodies to caprine arthritis-encephalitis virus using recombinant gag proteins.

The coding sequences of the core proteins p17 and p28 of caprine arthritis-encephalitis virus (CAEV) were amplified using the polymerase chain reaction and cloned into the plasmid expression vector p-GEX-2T. Both p17 and p28 were expressed as fusion proteins with glutathione S-transferase. The recombinant proteins were affinity purified from induced bacterial lysates using glutathione-agarose beads. The purified proteins were used in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies against CAEV in goat sera and milk samples. Three different ELISA tests were developed based on p17, p28 or the combination of these two recombinant proteins (p17 + p28). A comparison was made to an ELISA based on purified whole virus particles and to agar immunodiffusion test (AGID). Sera with conflicting results in the different ELISA tests were examined by Western blotting. There was a high correlation between the ELISA tests based on p17 + p28 recombinant proteins and whole virus ELISA, with an estimated kappa value of 0.92. Only 72-75% of the sera that tested positive in these two ELISA tests were positive in AGID. Antibodies to CAEV were detected in significantly more animals when serum samples were tested compared to milk samples. Based on the time and materials required to prepare the reagents, the recombinant based ELISA test was less expensive than the whole virus ELISA.

Animals↗
PubMed1994

An experimental study of primary feline immunodeficiency virus infection in cats and a historical comparison to acute simian and human immunodeficiency virus diseases.

Sixteen adolescent specific pathogen free cats were inoculated with the Petaluma strain of feline immunodeficiency virus (FIV) and two cats were then necropsied at each of 5, 10, 21, 28, 42, 56, 70, and 84 day time points following infection. Lymphadenopathy gradually increased starting at Day 10 and persisted for the duration. Gross clinical signs of fever, mild to severe malaise, anorexia, diarrhea, dehydration, and generalized soreness appeared around Day 42, peaked at Day 56, and disappeared by Days 70-84 post-infection. Leukopenia, associated initially with a mild lymphopenia and later by both a mild lymphopenia and a severe neutropenia, appeared 14-28 days following infection, troughed at Day 56, and persisted thereafter. The CD4+:CD8+ T cell ratio started to decrease around Day 28, reaching a nadir at Days 56-70. This decrease was due to a decline in the absolute numbers and percentage of CD4+ T cells and an increase in the percentage of CD8+ T cells. Significant histopathologic lesions included myeloid hyperplasia between Days 56-70 post-infection; thymitis with cortical involution and follicular hyperplasia starting at Day 42; lymphoid hyperplasia of peripheral and mesenteric nodes, spleen and tonsils beginning around Day 42; typhlitis most evident from Day 56 onward, and an interstitial nephritis and pneumonitis that was most intense after Day 42. Virus was isolated from peripheral blood mononuclear cells (PBMC) beginning 2 weeks post-infection, and plasma viremia appeared 1 week later. Plasma and PBMC-associated viremia peaked at 42-56 days following infection and decreased abruptly thereafter. Proviral DNA was detectable as early as 5 days after infection in blood leukocytes and after 10 days in other organs. The central nervous system, lungs, thymus, tonsils and mesenteric lymph nodes were the earliest sites of virus localization. Antibodies to the FIV capsid protein appeared 14 days following infection and reached peak levels by Days 42-56. Abnormalities occurring during the primary stage of FIV infection were consistent with those described for acute simian and human immunodeficiency virus-induced disease.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Effect of chronic feline immunodeficiency virus infection on experimental feline calicivirus-induced disease.

Acute feline calicivirus (FCV) infection caused a more severe disease in chronically feline immunodeficiency virus (FIV) infected than in non-FIV infected cats. FIV infected cats shed significantly higher amounts of FCV through their saliva after FCV challenge than the non-FIV infected cats. However, there was no difference in the duration of FCV shedding. None of the cats exposed to FCV developed chronic FCV carriage. Both groups of cats mounted similar titers of neutralizing antibodies to FCV. Although FIV infected cats started out with significantly lower total lymphocyte and neutrophil numbers than the non-FIV infected cats, the transient lymphopenia and neutrophilia attributable to the FCV infection was of similar intensity in both groups of animals. There was no evidence that the underlying FIV-related disease or viremia was influenced by acute FCV infection. Acute FCV infection did not significantly alter the CD4+/CD8+ T lymphocyte ratio in FIV infected compared to non-FIV infected cats. The ongoing humoral IgG response to FIV was not affected by the FCV infection. There was no significant change in the proportion of FIV infected peripheral blood mononuclear cells during 8 subsequent weeks after FCV challenge as determined by polymerase chain reaction.

Animals↗
PubMed1994

R-PEP-27, a potent renin inhibitor, decreases plasma angiotensin II and blood pressure in normal volunteers.

The hemodynamic and humoral effects of the specific human renin inhibitor R-PEP-27 were studied in six normal human subjects on low and high sodium intake diets. An intravenous infusion of R-PEP-27 (0.5 to 16 micrograms/min/kg body wt) reduced blood pressure in a dose-dependent fashion; the mean arterial blood pressure at the end of the infusion fell from 128 +/- 4/83 +/- 4 to 119 +/- 3/71 +/- 3 mm Hg (mean +/- SEM) (P < .01) during the low sodium intake diet. R-PEP-27 had no effect on blood pressure during the high sodium intake diet. R-PEP-27 significantly reduced plasma angiotensin II and aldosterone concentrations. The temporal response to R-PEP-27 suggests that it is a short-lived although highly potent competitive inhibitor of renin; this peptide is a valuable and specific physiologic probe of the renin-angiotensin system.

Adult↗
PubMed1994

Clinical aspects of the MASA syndrome in a large family, including expressing females.

We have evaluated, both clinically and by linkage analysis, a large family with 22 known affected males with the MASA syndrome (McKusick 303300). Clinical findings varied widely amongst the affected family members, with some appearing initially to have the MASA syndrome and others to have X-linked hydrocephalus (HSAS) (McKusick 307000). Important findings included the presence of adducted thumbs in two obligate carriers, learning problems or mild mental retardation in three females, two of whom were obligate carriers, and hydrocephalus with neonatal death in three females born to obligate carriers. X-inactivation analysis in lymphocytes from the two women with adducted thumbs revealed preferential inactivation of one X chromosome, suggesting that nonrandom X-inactivation may be responsible for clinical expression in females. The presence of HSAS in some individuals of this family and the MASA syndrome in others further supports the hypothesis that these two conditions are the result of a mutation in the same gene.

Child, Preschool↗
PubMed1994

Exercise-induced enhancement of immune function in the rat.

BACKGROUND: There have been many anecdotal reports that regular, moderate exercise confers some protective immunity against infection. There has been little scientific evidence to support this. It is also unclear whether training alters lymphocyte trafficking from the spleen to the periphery after a bout of exhaustive exercise. METHODS AND RESULTS: To determine the effect of moderate training on in vivo antibody production, using rats as an animal model, we gradually trained 18 rats using a swimming protocol for a 4-week period after injection and booster with Keyhole limpet hemocyanin antigen. There were 9 age-matched controls. At the conclusion of training, both groups underwent a short-term exhaustive swim. The trained group showed marked enhancement of IgM and IgG production. After short-term exercise, both groups had acute lymphocytosis, mainly T(suppressor)/cytolytic and natural killer cells with decreases in T(helper) (trained), B cells, and the Th-to-Ts ratio. The changes in the splenocyte subsets were the opposite of the changes in the peripheral blood. With respect to function, after exhaustive exercise, there was a slight increase in mitogenesis and interleukin-2 receptor expression to concanavalin A (untrained more than trained) compared with controls. CONCLUSIONS: Regular, moderate training enhances antibody production to specific de novo antigen both early and late. In addition, short-term exercise leads to selective release of immune cells from the spleen and results in slightly enhanced function of splenocytes. Direct stimulation by the sympathetic nervous system and catecholamines is the proposed mechanism for the changes seen after short-term exercise and possibly antibody production during training.

Animals↗
PubMed1993

The effect of age on the course of experimental feline immunodeficiency virus infection in cats.

Neonatal, young adult, and aged specific pathogen-free cats were experimentally infected with cat-passaged Petaluma strain of feline immunodeficiency virus. The primary stage of illness occurred 6-8 weeks following infection in cats of all ages, but it differed in severity and clinical signs. Generalized lymphadenopathy persisted for the entire 42-week study period in neonatally infected cats, was transient in young adults, but inapparent in aged cats. Only two aged cats became chronically and severely ill during the study. One aged cat died with severe necrotizing transmural enteritis, while a second developed chronic generalized staphylococcal pyoderma that was partially controlled with antibiotics. Neutropenia appeared 6-8 weeks following infection in cats of all ages, but was more severe in newborn and aged cats than in young adults. A persistent decrease in CD4+/CD8+ T lymphocyte ratios, due to both increased CD8+ and decreased CD4+ T lymphocytes, occurred in the neonatal and aged cats. Decreased CD4+/CD8+ T lymphocyte ratios in the young adult cats was due solely to decreased CD4+ T lymphocytes. Antibody response to FIV virus, as measured by ELISA to recombinant FIV p24 antigen, was lower in aged cats than the other age groups during the first 6 weeks after infection. Antibody levels were not significantly different among the three age groups thereafter. Although there are some differences between FIV infection of cats and HIV infection of human beings, age at infection influences the severity of disease in both species.

Aging↗
PubMed1993

Bepridil improves left ventricular performance in patients with angina pectoris.

Patients with coronary artery disease and angina pectoris have abnormalities of left ventricular (LV) diastolic performance. These abnormalities, which exist when the patients are at rest and not experiencing angina, are presumably secondary to abnormalities of intracellular calcium metabolism. Twenty-three patients with chronic exertional angina pectoris participated in a placebo-controlled, randomized, cross-over trial of bepridil hydrochloride. Angina frequency, nitroglycerin (NTG) consumption, and treadmill exercise capacity were assessed, and each patient underwent first-pass radionuclide cineangiography while receiving placebo or bepridil to assess LV performance. Bepridil decreased angina frequency from 8.5 +/- 0.6 to 4.4 +/- 1.5 episodes per week (p < 0.01) and NTG consumption from 7.2 +/- 2.4 to 3.6 +/- 1.5 tablets per week (p < 0.01). Total treadmill exercise time, time to onset of angina, and time to 1-mm ST segment depression increased significantly during bepridil therapy. Cardiac output (CO), stroke volume (SV), and ejection fraction (EF) increased at rest and during peak upright bicycle exercise. Peak ejection rate and peak filling rate increased, and time to peak ejection rate and time to peak filling rate decreased at rest and at peak exercise during bepridil therapy. In addition, early diastolic filling fraction increased and atrial filling volume decreased during bepridil treatment. Bepridil is effective as monotherapy for treatment of patients with exertional angina; its use is associated with increased exercise capacity and decreased angina frequency and NTG consumption as well as improved LV systolic and diastolic performance at rest and during peak exercise.

Adult↗
PubMed1993

Delayed seroconversion following naturally acquired caprine arthritis-encephalitis virus infection in goats.

One hundred eight milking goats from a dairy that had been using a modified caprine arthritis-encephalitis virus (CAEV) eradication program were tested for CAEV antibodies by serologic methods and for proviral CAEV DNA by use of polymerase chain reaction (PCR) technology. All goats were free of clinical symptoms of CAEV infection. Twenty-seven of the 108 goats were considered seropositive, on the basis of ELISA results. Proviral CAEV DNA was detected, using PCR techniques, in mononuclear leukocytes in blood samples obtained from 25 of the these 27 seropositive goats. Twenty of the 81 seronegative goats also had positive PCR test results. Ten of these goats seroconverted by 8 months later, and virus was readily isolated from mononuclear leukocytes in venous blood samples after the goats had seroconverted. Virus was also isolated from mononuclear leukocytes in blood samples collected from 4 of 11 goats that were seronegative, but had positive PCR test results. These results indicated that seroconversion can be delayed for many months following natural infection with CAEV. Delayed seroconversion appears to be a feature of CAEV infection, which may have direct implications for CAEV eradication programs and epidemiologic studies that rely on serologic methods to detect infected goats.

Animals↗
PubMed1992

Poor reception.

Patients who go private do so because their negative judgements of the NHS are based on media reports and hearsay, not facts or direct experience. To compete, say Joan Higgins and Rose Wiles, the NHS is going to have to unscramble its messages.

Attitude to Health↗
PubMed1992

Effects of antianginal therapy on left ventricular systolic and diastolic performance: comparison of the response to bepridil, propranolol, and diltiazem.

Abnormalities of left ventricular (LV) systolic performance develop during exercise in patients with coronary artery disease (CAD) as a result of ischemia-induced regional wall motion abnormalities. Like patients with hypertension and those with hypertrophic cardiomyopathy, patients with CAD display abnormalities of LV diastolic performance under basal conditions in the absence of ischemia. The purpose of these studies was to compare the effects of bepridil versus those of propranolol or diltiazem in patients with exertional angina pectoris. LV systolic and diastolic performance were assessed at rest and during peak upright bicycle exercise by first-pass radionuclide ventriculography. Compared with propranolol, bepridil increased exercise capacity, cardiac output, and stroke volume and decreased systemic vascular resistance. Compared with diltiazem, bepridil increased exercise capacity, peak filling rate, and early diastolic filling fraction and decreased systemic vascular resistance, heart rate, time to peak filling rate, and atrial filling volume. Bepridil therapy is associated with improved exercise capacity and decreased anginal frequency and nitroglycerin consumption. In addition, its use is accompanied by favorable changes in LV systolic and diastolic function at rest and during exercise. These changes are consistent with benefits resulting from resolution of myocardial ischemia as well as from positive lusitropic effects of bepridil on the ventricular myocardium.

Angina Pectoris↗
PubMed1992

Menopausal bone loss is partially regulated by dietary intake of vitamin D.

Five years ago we reported results from a cross-sectional study of the effect of nutritional factors on calcium-regulating hormones and bone loss in perimenopausal women. We found an inverse correlation between serum 25-hydroxyvitamin D (25OHD) and immunoreactive parathyroid hormone (PTH), and we postulated that over time, women with lower 25OHD would lose more bone because of increased bone remodeling induced by secondary hyperparathyroidism. We have followed 38 of these women for 5 years. Twenty-two have gone through menopause and we are reporting observations on these 22 subjects. Bone mineral analysis was performed twice a year at the distal and mid-radius using single-photon absorptiometry. The slope of the bone mineral content curve was calculated by least squares. Bone loss increased within 6 months of the rise in serum follicle stimulating hormone (FSH) to greater than 40 mIU/ml. We continued to see a negative correlation between 25OHD and PTH (r = -0.450, P = 0.03). Premenopause, PTH was negatively correlated with the proximal bone mineral content (PBMC) slope (-0.604, P = 0.002). The distal bone mineral content (DBMC) 5-year slope was correlated with dietary vitamin D (r = 0.509, P = 0.02), the higher the intake, the less negative the slope. The 5-year PBMC slope was negatively correlated with serum osteocalcin (OC) levels (r = -0.382, P = 0.08). Before menopause, the change in PBMC was positively correlated with OC (r = 0.450, P = 0.03). Postmenopause, the correlation with DBMC slope was negative (r = -0.506, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

25-Hydroxyvitamin D 2↗
PubMed1992

Stimulation of rat alveolar macrophage fibronectin release in a cadmium chloride model of lung injury and fibrosis.

Rats were exposed to saline or cadmium chloride (CdCl2) at 25, 100, or 400 micrograms/kg body weight by intratracheal instillation. At 3, 7, 14, and 28 days after exposure five animals/treatment were euthanized, the lungs were lavaged, and bronchoalveolar lavage fluid (BALF) was analyzed for lactate dehydrogenase (LDH), total protein, N-acetylglucosamindase (NAG), and cell number, type, and viability. Lung hydroxyproline concentration was characterized as a marker of lung collagen. Alveolar macrophages (AM) obtained in BALF were cultured and the release of fibronectin and TNF was determined. Lung tissue was examined microscopically at 28 and 90 days after exposure. Exposure to CdCl2 resulted in lung injury and inflammation demonstrated by increases in BALF LDH, total protein, NAG, and inflammatory cells. AM TNF release was not significantly changed by CdCl2 treatment. All doses of CdCl2 stimulated AM fibronectin secretion, a response which persisted throughout the 28-day postexposure period examined. Pulmonary fibrosis was demonstrated biochemically and/or histologically (trichrome staining tissue) at all CdCl2 dose levels. The association of CdCl2-induced AM fibronectin release with lung fibrosis confirms and extends previous observations relating AM-derived fibronectin to the development of interstitial lung disease and provides further evidence that the persistent increase in AM fibronectin release represents an early indicator of fibrosis.

Animals↗
PubMed1992

Interaction of acute feline herpesvirus-1 and chronic feline immunodeficiency virus infections in experimentally infected specific pathogen free cats.

Cats with or without chronic feline immunodeficiency virus (FIV) infection were exposed to feline herpesvirus, type 1 (FHV-1). FIV infected cats became sicker than non-FIV infected cats and required more supportive treatment. However, there were no differences in the length of their illness or in the levels and duration of FHV-1 shedding. FHV-1 infection caused a transient neutrophilia at Day 7 with a rapid return to preinfection levels. The neutrophilia coincided with a transient lymphopenia that was accompanied by a decline in both CD4+ and CD8+ T-lymphocytes. A brief decrease in the CD4+/CD8+ T-lymphocyte ratio occurred at Day 14 in both FIV infected and non-infected cats. This decrease was mainly the result of an absolute and transient increase in CD8+ T-lymphocytes. CD4+ and CD8+ T-lymphocyte numbers and CD4+/CD8+ T-lymphocyte ratios returned to baseline within 4-8 weeks in both FIV infected and non-infected cats. FIV infected cats produced less FHV-1 neutralizing antibodies during the first 3 weeks of infection than non-FIV infected animals. The IgM FHV-1 antibody response was depressed in FIV infected cats whereas the IgG antibody response was unaffected. FHV-1 infection evoked a comparable transient loss of lymphocyte blastogenic responses to concanavalin A and pokeweed mitogen in both FIV infected and non-infected cats. However, response to pokeweed mitogen took longer to return to normal in FIV infected animals. Lymphocytes from FIV infected cats had a greater and more sustained proliferative response to FHV-1 antigen than non-FIV infected cats. The ongoing IgG antibody response to FIV was not affected by FHV-1 infection.

Acute Disease↗
PubMed1992

Effects of fosinopril on cardiac function in patients with hypertension. Radionuclide assessment of left ventricular systolic and diastolic performance.

Numerous pharmacologic agents are capable of lowering the blood pressure of hypertensive patients; however, each drug has a characteristic side effect profile and effect on cardiac performance. In this study, the hemodynamic effects of the angiotensin converting enzyme inhibitor fosinopril were assessed at rest and at peak upright bicycle exercise by first-pass radionuclide cineangiography in 12 patients with essential hypertension. Fosinopril reduced blood pressure at rest in the seated position from 152/101 to 131/85 mm Hg (P less than .01) and at peak exercise from 206/103 to 184/91 mm Hg (P less than .01). Fosinopril therapy was associated with an increase in stroke volume and cardiac output and a decrease in systemic vascular resistance at rest and during peak exercise. Both peak ejection rate and peak filling rate increased significantly at rest during fosinopril therapy. The unique cardiotropic response to fosinopril may reflect its effects on the myocardial renin-angiotensin system, and suggests that this agent may offer a therapeutic advantage compared with other angiotensin converting enzyme inhibitors.

Adolescent↗
PubMed1992

Comparison of the cardiac and hemodynamic effects of lisinopril and atenolol in patients with hypertension: therapeutic implications.

The antihypertensive and hemodynamic effects of lisinopril and atenolol were evaluated in 21 patients with mild-to-moderate essential hypertension. Left ventricular systolic and diastolic performances were assessed prior to and following treatment by first-pass radionuclide cineangiography at rest and during peak upright bicycle exercise. Both lisinopril and atenolol treatment significantly reduced the blood pressure. Lisinopril therapy was associated with a reduction in systemic vascular resistance and left ventricular end-diastolic and end-systolic volumes but no change in stroke volume, cardiac output, peak ejection rate, peak filling rate, time to peak ejection rate, or time to peak filling rate. In contrast, atenolol therapy was associated with an increase in end-diastolic volume and stroke volume but no change in cardiac output; the left ventricular peak ejection and peak filling rates were decreased by atenolol treatment. Although both lisinopril and atenolol each significantly reduced the blood pressure, lisinopril had no effect on left ventricular systolic or diastolic performance; in contrast, atenolol decreased both systolic and diastolic parameters of ventricular performance. Left ventricular function may be affected in significantly different ways despite apparent similarities in blood pressure control in patients who respond to angiotensin converting enzyme inhibition or beta-adrenergic receptor blockade. Differences in hemodynamic response to an antihypertensive agent may be important in the selection of a drug for the treatment of subsets of patients with cardiac function abnormalities.

Adult↗