Search PubMed⌕ Search

Biomedical subjects

M C Harris

Publications and source records attributed to M C Harris.

At least 55 records · Page 3Linked to original sources

Activation of hypothalamic arcuate but not paraventricular neurons following carotid body chemoreceptor stimulation in the rat.

The effect of carotid body chemoreceptor stimulation on 292 neurons in midline hypothalamic nuclei has been examined electrophysiologically in ethyl carbamate/sodium pentobarbitone anaesthetized rats. Experiments demonstrated that specific stimulation of carotid body chemoreceptors activates a small group (16) of neurons in the mediobasal hypothalamic arcuate nucleus, but has no effect on neurons (157) in the hypothalamic paraventricular nucleus or the anterior hypothalamus. Of 16 arcuate neurons activated by the stimulus, six projected to the median eminence and three projected to the dorsal medulla, as defined by antidromic invasion. Three of the neurons activated from the carotid body also showed a resting discharge that was linked with ventilation rate, suggesting that the arcuate nucleus may have some involvement with respiratory processing. The activation of neurons projecting to the median eminence implies that the release of adenohypophyseal hormones may also be influenced by carotid body chemoreceptors.

Animals↗

Effects of dexamethasone and indomethacin on elastase, alpha 1-proteinase inhibitor, and fibronectin in bronchoalveolar lavage fluid from neonates.

Elastase activity and concentrations of alpha 1-proteinase inhibitor, albumin, and fibronectin were measured in bronchoaleolar lavage (BAL) fluid from ventilated lungs in preterm neonates with lung disease before and after treatment with dexamethasone or indomethacin. Treatment with dexamethasone was associated with a significant decrease in BAL elastase activity but no change in fibronectin, albumin, or alpha 1-proteinase inhibitor concentrations. In contrast, treatment with indomethacin was associated with an increase in BAL elastase activity and fibronectin concentration, with no change in albumin or alpha 1-proteinase inhibitor concentrations. Control groups showed no changes in these BAL fluid biochemical markers during a similar time period. These data indicate that treatment with corticosteroids decreases lung inflammation as measured by BAL elastase activity. Corticosteroid treatment may not inhibit the development of pulmonary fibrosis, because fibronectin concentrations in BAL fluid were unaffected. Indomethacin treatment may augment lung inflammation and fibrosis by increasing BAL elastase activity and fibronectin concentration.

Acute-Phase Proteins↗

Amniotic fluid fibronectin concentrations with advancing gestational age.

Fibronectin, a large-molecular-weight glycoprotein present on cell surfaces and in human plasma, promotes cell adhesion and may modulate reticuloendothelial clearance of particulate debris and bacteria. Amniotic fluid is known to contain a heavily glycosylated variety of fibronectin, and cells derived from amniotic fluid synthesize and secrete fibronectin in tissue culture. The purpose of this study was to determine the relationship between the concentration of fibronectin in amniotic fluid and gestational age. Amniotic fluid samples, obtained from 54 women whose pregnancies ranged in gestation from 15-40 weeks, demonstrated a significant decrease in fibronectin levels with increasing duration of pregnancy (r = -0.70). Diminished concentrations of amniotic fluid fibronectin in the latter stages of pregnancy may represent either decreasing synthesis by amniocytes or a dilutional effect from fetal urine.

Amniotic Fluid↗

Activation within dorsal medullary nuclei following stimulation in the hypothalamic paraventricular nucleus in rats.

The influence of the hypothalamic paraventricular nucleus (PVN) on neurones in the dorsal medulla has been examined in 71 urethane/sagatal-anaesthetised rats. Of 536 neurones localised and tested for responses to electrical stimulation of both the vagus and/or the PVN, 378 were synaptically or antidromically activated following vagal stimulation 72 of which were synaptically activated by stimulation within PVN. The majority of those were located at the border between NTS and dorsal motor nucleus of the vagus in caudal NTS. None showed cardiac or ventilatory rhythm. Neurones showing such rhythms were not affected from PVN. Of 89 neurones in dorsal motor nucleus of the vagus, ten were synaptically activated and two synaptically depressed from PVN. PVN activated neurones in NTS tested for responses to stimulation of arterial baroreceptors and carotid body chemoreceptors were either unaffected or inhibited, but gastric inflation excited them. The results suggest a powerful PVN influence on the dorsal medulla, which is largely confined to the ventral and caudal NTS. There is little evidence for an effect on neurones with a cardiovascular function, but the abdominal vagal influence suggests a link with feeding.

Animals↗

Indirect enzyme-linked immunosorbent assay for measurement of human immunoglobulins E and G to purified cow's milk proteins: application in diagnosis of cow's milk allergy.

An indirect double-antibody enzyme-linked immunosorbent assay (ELISA) was developed for the measurement of human immunoglobulin E (IgE) and IgG to the cow's milk proteins (CMP) alpha-casein, alpha-lactalbumin, and beta-lactoglobulin. Human serum albumin was used as the negative-antigen control. Rabbit anti-human IgE or IgG served as the primary antibody, and horseradish peroxidase-conjugated swine anti-rabbit immunoglobulin served as the secondary antibody. Positive control sera were obtained from patients with well-documented histories of cow's milk allergy, while negative control sera were obtained from cord bloods of healthy full-term infants and from normal adult volunteers without known milk allergy. Test sera were obtained from 41 children (ages, 3 months to 13 years; average age, 2.6 years) with suspected cow's milk allergy and clinical manifestations that included wheezing, rhinitis, atopic dermatitis, urticaria, or gastrointestinal disturbances. The patients were simultaneously evaluated by prick skin testing with scratch test antigen to whole CMP. Although only 13 (32%) of the 41 patients were positive by the prick skin test, 25 (61%) were positive by the IgE ELISA. Of the 25 IgE ELISA-positive patients, 20 were also positive by the IgG ELISA. There was concordance of positive results between skin testing and the IgE ELISA in only 9 patients (22%), and there was concordance of negative results in 12 patients (29%). Discordant results were observed in 20 patients (49%). These results indicate that the ELISA is more sensitive than prick skin testing in the identification of individuals with elevated levels of IgE to CMP.

Adult↗

Diminished polymorphonuclear leukocyte adherence and chemotaxis following protein-calorie malnutrition in newborn rats.

Recent advances in neonatal care have permitted the survival of very low birth weight infants who are difficult to nourish, and ultimately develop clinical and biochemical signs of malnutrition. These infants may be at greater risk for nosocomial infection than normally nourished hosts. We have compared neutrophil adherence and chemotactic responses in a newborn rat model of protein-calorie malnutrition. Wistar rats at 14 days gestation received either a normal (24% protein) or isocaloric (2.5% protein) diet. On day 5, rat pups were divided into three groups: pups allowed to nurse on their own dam (normal); normally nourished pups foster nursed onto a malnourished mother (depleted); or malnourished pups foster nursed to a normal dam (repleted). Granulocytes from depleted pups demonstrated significantly diminished adherence and chemotaxis when compared to normal or repleted pups. Thus, abnormalities of neutrophil function in malnourished newborn rats may contribute to increased susceptibility to bacterial infection.

Animals↗

Interleukin-1 activity from human cord blood monocytes.

Cord blood monocyte synthesis of IL-1 was investigated by using a thymocyte proliferation assay. Monocytes from 27 infants ranging in gestation from 31 to 41 weeks (mean 38.9, SE 0.54) with birthweights from 1.20 to 4.31 kg (mean 3.24, SE 0.13) were isolated from cord blood; 2 x 10(5) cells/ml were plated in 15 mm wells and stimulated with 10 micrograms/ml LPS (E. coli). Control cultures contained medium alone. Supernatants were harvested after 24 hr and tested in a C3H/HeJ mouse thymocyte proliferation assay. The mean response for 27 cord monocyte samples at 24 hr was 14,142 cpm (SE 1,499), not significantly different than that for cells obtained from eight normal adult volunteers (15,137 cpm, SE 3,535). Vaginally delivered infants with perinatal complications such as amnionitis, fetal distress, or early sepsis had significantly increased unstimulated activity (5,139 vs 1,331 cpm) compared to samples from normal infants, whereas stimulated activity was not significantly different (16,219 vs 12,261 cpm). Thus, the IL-1 response to lipopolysaccharide is intact in newborn human monocytes and there is evidence of an increased unstimulated activity following neonatal complications.

Cells, Cultured↗

Tracheal lavage and plasma fibronectin: relationship to respiratory distress syndrome and development of bronchopulmonary dysplasia.

Plasma for fibronectin determinations was obtained from 39 neonates with uncomplicated respiratory distress syndrome (RDS) and from 15 infants with RDS who developed bronchopulmonary dysplasia (BPD). Tracheal lavage fibronectin and albumin concentrations were measured in 15 infants with RDS and 15 with BPD. Control plasma fibronectin values were obtained from 20 healthy preterm infants on days 1, 2, 3, 14, and 30 of life. Control tracheal lavage fibronectin and albumin concentrations were measured in 17 neonates of various gestational ages who required tracheal intubation for nonpulmonary indications. Mean plasma fibronectin concentrations from patients with RDS was 121 +/- 11 micrograms/ml on days 1, 2, and 3, versus control level of 163 +/- 12 micrograms/ml (P less than 0.01). Mean tracheal lavage fibronectin/albumin ratio was 3.8 +/- 0.6 ng per microgram of albumin on days 1 to 5 for infants with RDS, versus control level of 5.6 +/- 3.6 (P = NS). Tracheal lavage fibronectin/albumin ratio from patients with BPD was elevated at 16.3 +/- 5.0 ng fibronectin per microgram of albumin on days 14 to 21, and 23.6 +/- 7.4 on day 30 (P less than 0.05 versus control and and versus RDS days 1 to 10). Low plasma fibronectin concentrations early in RDS may contribute to the development of pulmonary capillary leak. High tracheal lavage fibronectin levels may foster the development of pulmonary fibrosis in patients with BPD.

Albumins↗

Effect of fibronectin on adherence of neutrophils from newborn infants.

Neutrophils (polymorphonuclear leukocytes [PMNs]) from infants and adults increased in adherence over a 20-min incubation as measured in a morphological assay. At each time point, PMNs from healthy infants had significantly diminished adherence when compared with those of adults; PMNs from sick newborn infants showed intermediate adherence values. Moreover, PMNs from healthy infants had significantly diminished membrane fluorescence for fibronectin when compared with those of adults. Preincubation with exogenous fibronectin did not augment the adherence of PMNs from infants or adults. Deficient adherence of PMNs from newborns may be related to decreased membrane fibronectin.

Adult↗

The detection of streptococcal antigens using monoclonal antibodies.

Recent advances in hybridoma technology have allowed the development of homogeneous immunologic reagents of defined specificity, activity, and reproducibility. During the last few years, the number of monoclonal antibodies directed against bacteria has increased exponentially, and research investigations have focused on the use of monoclonal antibodies for the diagnosis and therapy of infectious diseases. Monoclonal antibody technology offers a rapid, specific diagnosis of bacterial infection, long before culture results are available. We have described the use of monoclonal antibodies for the detection of group B streptococcal (GBS) infections in mothers and infants at risk to develop invasive GBS disease. Specifically, we have used the anti-GBS monoclonal antibodies to detect GBS colonization, serotype bacterial isolates in the laboratory, and identify GBS antigens in body fluid specimens. We have also discussed the use of anti-GBS monoclonal antibodies to confer protection against fatal infection in mice. Monoclonal antibodies against group A streptococcus and Streptococcus pneumoniae have also been developed with the potential for the rapid diagnosis of serious and often life-threatening infections, particularly in immunocompromised individuals. With further refinements in monoclonal antibody technology in the future, streptococcal hybridomas may replace standard culture techniques for bacterial identification in the microbiology laboratory.

Adolescent↗

Vancomycin dosage in pediatrics reconsidered.

Vancomycin hydrochloride levels were studied in 44 children (age range, 10 days to 10 years). These children received doses of vancomycin within current recommendations. Major variations in vancomycin levels were demonstrated in similar age groups and dosage regimens. For patients in the first month of life, second month of life, and older ages, respectively, 70%, 39%, and 30% of the peak determinations and 53%, 50%, and 23% of the trough determinations were greater than the desired level. Potentially toxic levels were found in eight patients.

Age Factors↗

The afferent pathway for carotid body chemoreceptor input to the hypothalamic supraoptic nucleus in the rat.

The pathway for chemoreceptor input to hypothalamic supraoptic nuclei has been examined in anaesthetised lactating and non-lactating rats. In lactating rats, the increase in intramammary pressure following bilateral carotid occlusion, which is probably mainly due to vasopressin, was abolished by lesions in the septum, but not by lesions in more caudal regions of the hypothalamus. In non-lactating rats, electrophysiological experiments demonstrated that the input from carotid body chemoreceptors to phasically-discharging supraoptic neurones is ipsilateral only. The effects of chemoreceptor stimulation on the neurones can be mimicked by electrical stimulation within the medial preoptic area and anterior hypothalamus in a region medial and rostral to the supraoptic nuclei. Lesions within this region abolish the chemoreceptor input to the supraoptic nuclei, but leave the baroreceptor input intact. It is proposed that chemoreceptor afferents to the supraoptic nuclei pass in the lateral hypothalamus to the region of the septum where they turn medially and descent through the medial part of the rostral hypothalamus. The results are discussed in terms of the general role of the chemoreceptor reflex and, more specifically, with respect to the possible significance of vasopressin in the control of arterial blood pressure.

Afferent Pathways↗

Lesions of the locus coeruleus abolish baroreceptor-induced depression of supraoptic neurones in the rat.

Urethane-anaesthetized rats were used to investigate the influence of lesions within the locus coeruleus on the inhibition of phasically discharging supraoptic neurones that normally follows the activation of arterial baroreceptors. Carotid sinus baroreceptors were stimulated by the inflation of a blind sac of the carotid bifurcation. A general activation of arterial baroreceptors was evoked by increasing arterial blood pressure following the intravenous injection of the pure alpha-adrenoreceptor agonist phenylephrine. The locus coeruleus of one side only was destroyed either by thermal (radio-frequency) lesions, or by the injection of 6-hydroxydopamine (1 microliter, 0.5 mg/ml). The extent of each lesion was assessed histologically in stained tissue and with fluorescence histochemistry. Lesions in locus coeruleus abolished all baroreceptor input to supraoptic neurones on the side ipsilateral to the lesion. The lesions had no effect on the cardiovascular responses to the stimulus, and did not abolish the excitation of supraoptic neurones after ipsilateral carotid body chemoreceptor activation. 6-Hydroxydopamine lesions (1 microliter, mg/ml) in the rostral part of the ventrolateral A1 catecholamine neurones were less consistent in their abolition of baroreceptor input to the supraoptic nucleus. When the input from ipsilateral carotid sinus baroreceptors was abolished, there was an equivalent effect on the influence of the carotid body chemoreceptors. Input from other arterial baroreceptors, activated by phenylephrine injection, was not affected. From these results, it is proposed that the baroreceptor-induced depression of-phasically discharging supraoptic neurones is mediated via a direct noradrenergic input from the locus coeruleus.

Action Potentials↗

Diminished bactericidal capacity for group B Streptococcus in neutrophils from "stressed" and healthy neonates.

This study compared the bactericidal capacity of polymorphonuclear leukocytes (PMNs) from neonates and adults for type Ic group B Streptococcus (GBS), and examined the effect of severe stress on the bactericidal capacity of PMNs from newborn infants. PMNs were obtained from three study groups: 26 adults, 13 healthy neonates (cord blood), and 29 stressed neonates. Stress was defined as an acute respiratory illness or bacterial infection requiring assisted ventilation. Bacterial killing was assessed using a fluorochrome microassay and PMNs adherent to glass coverslips. PMNs from stressed infants killed significantly fewer GBS than PMNs from adults (P less than 0.001 at both time points). PMNs from healthy infants also demonstrated reduced killing compared with adults (P less than 0.01 at 60 min; P less than 0.001 at 90 min). There was no significant difference in bacterial killing between stressed and healthy neonates and no correlation between bactericidal capacity and age at time of study, gestational age, birth weight, peripheral leukocyte count, or Apgar scores. Therefore, the bactericidal capacity for GBS by PMNs from neonates is diminished; however, it is not further compromised by stress.

Adult↗

Neonatal septicemia.

Explore the source record for details and available documents.

Anti-Bacterial Agents↗