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Biomedical subjects

M Carroll

Publications and source records attributed to M Carroll.

At least 19 recordsLinked to original sources

Isolation of anonymous DNA markers for human chromosome 22q11 from a flow-sorted library, and mapping using hybrids from patients with DiGeorge syndrome.

DiGeorge syndrome (DGS) is a human developmental defect of the structures derived from the third and fourth pharyngeal pouches. It apparently arises due to deletion of 22q11. We describe a strategy for the isolation of DNA probes for this region. A deleted chromosome 22, which includes 22q11, was flow-sorted from a lymphoblastoid cell line of a patient with cat eye syndrome and used as the source of DNA. A DNA library was constructed from this chromosome by cloning into the EcoR1 site of the vector Lambda gt10. Inserts were amplified by PCR and mapped using a somatic cell hybrid panel of this region. Out of 32 probes, 14 were mapped to 22q11. These probes were further sublocalised within the region by dosage analysis of DGS patients, and by the use of two new hybrid cell lines which we have produced from DGS patients. One of these lines (7939B662) contains the altered human chromosome segregated from its normal homologue. This chromosome 22 contains an interstitial deletion in 22q11, and will be useful for localising further probes to the DGS region.

Base Sequence

Protection against hippocampal CA1 cell loss by post-ischemic hypothermia is dependent on delay of initiation and duration.

The temporal constraints of protection of neuronal damage by post-ischemic hypothermia was investigated in the gerbil model of global ischemia. Three experimental paradigms were used: 1) Hypothermia was initiated prior to ischemia followed by warming to normothermia immediately post ischemia; 2) Hypothermia of different durations was initiated immediately after reflow and 3) Six hours of hypothermia was initiated at various times following reperfusion. Hypothermia during 5 minutes of ischemia followed by warming to normal body temperature immediately post ischemia resulted in near complete protection of the hippocampus from CA1 cell loss. Hypothermic durations of 1/2, 1, 2, 4, and 6 hours beginning immediately following reperfusion resulted in progressively increased protection from ischemic damage (6 +/- 6%, 21 +/- 10%, 34 +/- 15%, 75 +/- 16% and 77 +/- 12%, respectively). Six hours of hypothermia delayed for 1 hour after reperfusion resulted in 49 +/- 9% protection. No reduction of ischemic damage was observed if 6 hours of hypothermia was delayed for 3 hour after reflow. These data suggest that: 1) Hypothermia during ischemia protects the brain from damage; 2) Hypothermia initiated immediately following reperfusion must have a duration of 2 hours or more to be effective and 3) Six hours of hypothermia is effective if initiated within 1 hour of reperfusion.

Animals

Early changes in T lymphocytes recovered by bronchoalveolar lavage after local allergen challenge of asthmatic airways.

To assess the role of T lymphocytes in the initiation of the allergic asthmatic response we have investigated T-cells subsets and their activation markers in bronchoalveolar lavage (BAL) fluid recovered 10 min after local challenge of the bronchial mucosa with allergen or saline. Endobronchial challenge was performed in 13 mildly atopic asthmatic patients (FEV1% predicted range, 78.2 to 116.5) and 10 normal volunteers. In all of the asthmatics but in none of the normal subjects allergen but not saline exposure resulted in visible bronchoconstriction. Analysis of BAL by flow cytometry showed no differences in the overall number of T cells (CD3+) and their CD4+ and CD8+ subsets per milliliter of BAL between the groups of normal subjects and asthmatics. However, within 10 min of allergen challenge, in the asthmatics but not in the normal subjects, there occurred a significant loss of CD3+ cells (p less than 0.01) comprising mostly CD4+ (p less than 0.05) but also CD8+ cells, with a consequent decrease in the CD4:CD8 ratio. At this early time point no differences in the extent of expression of the T-cell activation markers, IL-2 receptor, and HLA-DR were found. These results provide evidence to support a role of T lymphocytes early in the allergen-induced inflammatory response in asthma.

Adult

Intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) expression in the bronchial mucosa of normal and asthmatic subjects.

Bronchial lavage and biopsy studies suggest the involvement of eosinophils and T-lymphocytes in allergic inflammation in asthma. There is evidence suggesting that the expression of adhesion molecules on endothelial cells and of their receptors on leucocytes is involved in this process. To investigate these mechanisms we have obtained bronchial mucosal biopsies from 10 normal subjects and from 10 symptomatic atopic asthmatics. Six of the asthmatics were re-biopsied after 6 weeks of inhaled beclomethasone dipropionate (BDP) during which time their clinical response was monitored. Frozen sections were stained by the immunoperoxidase method using monoclonal antibody (MoAb) 6.5B5 to identify expression of intercellular adhesion molecule (ICAM-1) and MoAb 1.2B6 for endothelial leucocyte adhesion molecule (ELAM-1). Araldite-embedded sections were also stained for eosinophils using MoAb EG2 to identify eosinophilic cationic protein (ECP). A significant mucosal eosinophilia was apparent in the asthmatic but not in the normal biopsies. Immunostaining for ICAM-1 was observed in both the epithelium and endothelium and ELAM-1 in endothelium, with no significant differences being apparent between the asthmatic and normal subjects. Topical BDP markedly reduced the mucosal eosinophilia without affecting the expression of either adhesion molecule. Using this method, we conclude that there is basal expression of ICAM-1 and ELAM-1 in normal human bronchial mucosa, which is not significantly different from that in asthmatics, and that it is insensitive to suppression with corticosteroids at an inhaled dose that causes clinical improvement.

Adult

Glycoprotein expression in mouse cerebellum: effects of inhibitors of N-linked glycosylation.

1. Explants of cerebellum from foetal mouse were cultured in vitro for 10 days in the presence of one of 4 inhibitors of N-linked glycosylation (castanospermine, deoxymannojirimycin, swainsonine, and tunicamycin). 2. The effects of the inhibitors were compared with respect to: (a) the activity of enzymes involved in glycoprotein biosynthesis and degradation; (b) the expression of N-linked glycoproteins; (c) the morphology and ultrastructure of the treated cerebellar explants.

1-Deoxynojirimycin

Glycoprotein expression in mouse cerebellum: effects of inhibitors of vesicle function.

1. Explants of cerebellum from foetal mouse were cultured in vitro for 10 days in the presence of one of 5 inhibitors of vesicle function (ammonia, brefeldin A, carbonyl cyanide m-chlorophenylhydrazone, diethylcarbamazine, and monensin). 2. The effects of the inhibitors were compared with respect to: (a) the activity of enzymes involved in glycoprotein biosynthesis and degradation; (b) the expression of N-linked glycoproteins; (c) the morphology and ultrastructure of the cerebellar explants.

Ammonia

Renal, hormonal, and fluid shift responses to ANP during head-out water immersion in awake dogs.

Renal responses to low doses of atrial natriuretic peptide (ANP) may be potentiated during water immersion-induced central hypervolemia. To test this hypothesis, ANP was infused in awake dogs in doses of 0, 5, and 25 ng.kg-1.min-1 either when the dogs were in air or during head-out water immersion (WI) under thermoneutral conditions (37 degrees C). In general, there were greater diuretic (V) and natriuretic responses (UNaV) at the same level of plasma ANP in WI, with the slopes (or sensitivities) of V and UNaV in relation to plasma ANP levels being significantly increased during WI. Plasma renin activity decreased only during WI and was significantly correlated with both V and UNaV only during WI. Plasma and urinary arginine vasopressin levels were unchanged during WI. Infusion of ANP prevented the usual decline of hematocrit that occurs during WI. These results support the view that the renal sensitivity to ANP is augmented during the plasma volume expansion of WI. In addition, ANP may attenuate the transcapillary fluid shift that occurs during WI.

Animals

Serum total cholesterol: HDL cholesterol ratios in US white and black adults by selected demographic and socioeconomic variables (HANES II).

BACKGROUND: Framingham Study findings suggest that total cholesterol (TC):High density lipoprotein cholesterol (HDL-C) ratio is a useful summary of the joint contribution of TC and HDL-C to coronary heart disease (CHD) risk. Information on the distribution of TC:HDL-C in the US population is limited to selected populations and the relationship of the ratio distribution and its correlates has received little attention. METHOD: TC/HDL-C ratios were examined in a representative sample of the United States adult population ages 20 to 74 years, between February 1976 and February 1980 during NHANES II, using stratification and multivariate regression analyses. RESULTS: Age-adjusted mean ratios were higher in men compared with women and were higher in Whites compared with Blacks. White men had the highest TC/HDL-C mean ratios. These relationships remained after stratification by age, education, body mass index, alcohol use, cigarette smoking, and physical activity. Using multivariate analyses, the ratios were positively related to BMI, age, and smoking; and negatively related to female sex, alcohol use, being Black, and physical activity. CONCLUSIONS: Using a ratio reference point of greater than or equal to 4.5 from the Framingham study, at least an estimated 44 million persons ages 25 to 74 years in the US were found to be at higher risk of developing coronary heart disease.

Adult

A method for delivery of precise doses of smoked cocaine-base to humans.

Despite increasing smoked cocaine-base use, there have been relatively few parametric studies in this area. The major reason for the limited number of studies is the lack of a simple procedure for the administration of precise doses of smoked cocaine-base to human volunteers. This paper describes a new method that allows for the delivery of precise doses of smoked cocaine-base. A complete description of the method and the precision of the administration procedure are presented. Furthermore, a study is described which was undertaken to determine: 1) the reproducibility of peak blood cocaine levels when the same dose of cocaine was given on two separate occasions; and 2) the dose-related effects on smoking topography, biochemical, physiological and subjective measures. Subjects (N = 5) were administered three doses of cocaine-base (10, 20 and 40 mg). Four subjects were given repeated doses of cocaine-base. Subjects were blind to the dose and in most cases randomly assigned to different doses. The results showed: 1) a significant correlation of peak whole blood cocaine concentrations among similar doses within subjects (r = .99); 2) no significant effects of dose on smoking topography; and 3) significant dose effects for whole blood cocaine concentrations, heart rate and systolic blood pressure.

Adult

Dietary patterns of U.S. children: implications for disease prevention.

Nutritional data from the second National Health and Nutrition Examination Survey (NHANES II) were analyzed to assess dietary patterns of a representative sample of U.S. children and youth ages 1-17 years. The data show that the average U.S. child's diet is relatively high in total and saturated fat and low in the ratio of polyunsaturated to saturated fat. These dietary patterns deviate from current dietary recommendations for the prevention of cardiovascular diseases. The percentage contributions of specific macronutrients to total energy intake (in kilocalories) were total fat, 35-36%; total carbohydrates, 49-51%; and protein, 15-16%. This is in contrast to current expert recommendations for children of 30% of kilocalories as total fat, 55% as carbohydrates, and 15% as protein. The observed intake of saturated fat in U.S. children was 13% of kilocalories vs a recommended level of 10% of kilocalories. The observed ratio of polyunsaturated to saturated fat intake was 0.4 vs a recommended ratio of 1.0. There were important racial differences in fat intakes, with blacks generally having higher cholesterol and total fat intakes. White children generally consumed more of their calories as carbohydrates than did black children, but there were no differences in protein intakes between the two groups. In summary, these data suggest that the average U.S. child's diet deviates from recommended dietary guidelines for fat and cholesterol intakes. Black children's dietary patterns appear less favorable for cardiovascular health than those of white children. However, the data also show that achieving recommended dietary intake patterns probably will not require drastic changes in the U.S. child's diet.

Adolescent

Glycoprotein expression in foetal and adult mouse cerebellum.

1. Explants of cerebellum from foetal mouse were cultured in vitro for up to 12 days. Some glycoprotein components displayed time-dependent changes in concentration in the cultured explants. 2. The specific activity of several enzymes involved in the biosynthesis or degradation of N-linked glycoproteins, increased markedly in the cerebellar explants as a function of time in culture. 3. Glycoprotein expression in foetal mouse cerebellum is compared with that in the adult tissue.

Animals

Hypertension prevalence and the status of awareness, treatment, and control in the Hispanic Health and Nutrition Examination Survey (HHANES), 1982-84.

The prevalence rates of hypertension among adult (ages 18-74) Mexican Americans, Cuban Americans, and Puerto Ricans were estimated using data from the 1982-84 Hispanic Health and Nutrition Examination Survey (HHANES). Hypertension is defined as diastolic greater than or equal to 90 mm Hg, or systolic greater than or equal to 140 mm Hg, or currently taking antihypertensive medication. Among Mexican Americans in the Southwestern United States, 16.8 percent of the males and 14.1 percent of the females were found to be hypertensive. Among Cuban Americans in Dade County, Florida 22.8 percent of the males and 15.5 percent of the females were hypertensive. Among Puerto Ricans in the New York City area 15.6 percent of the males and 11.5 percent of the females were hypertensive. The age-adjusted rates are significantly lower than comparable rates for Whites and Blacks as measured in the second National Health and Nutrition Examination Survey (NHANES II), 1976-80. Control of hypertension in the HHANES populations fall short of the 1990 Objectives for the Nation established by the US Public Health Service 60 percent (34 percent controlled Mexican American hypertensives, 27.8 percent controlled Cuban American hypertensives, and 29 percent controlled Puerto Rican hypertensives.

Adult

Prevalence of chronic bronchitis among US Hispanics from the Hispanic Health and Nutrition Examination Survey, 1982-84.

In the Hispanic Health and Nutrition Examination Survey (HHANES), Puerto Ricans had a higher age-adjusted prevalence of self-reported chronic bronchitis (2.9 percent, 95% CI = 2.2, 3.6) than Mexican Americans (1.7 percent, 95% CI = 1.3, 2.1) or Cubans (1.7 percent, 95% CI = 0.9, 2.5). The prevalence of chronic bronchitis was at least 2 times higher in smokers as compared to nonsmokers among Puerto Ricans and Cubans, but not for Mexican Americans.

Adolescent

Serum lipids and lipoproteins of Hispanics, 1982-84.

This report presents descriptive data for serum lipids and lipoproteins by age, sex, and selected socioeconomic variables. This information is from the Hispanic Health and Nutrition Examination Survey, a sample survey of selected groups of civilian noninstitutionalized Hispanic persons residing in selected area of the United States, that was conducted during the period 1982-84.

Adult