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Biomedical subjects

A M Moore

Publications and source records attributed to A M Moore.

At least 19 recordsLinked to original sources

Cutting edge: secondary lymphoid-tissue chemokine (SLC) and CC chemokine receptor 7 (CCR7) participate in the emigration pathway of mature dendritic cells from the skin to regional lymph nodes.

Dendritic cells (DCs) emigrate to regional lymph nodes (LNs) during immune responses via afferent lymphatic channels. Secondary lymphoid-tissue chemokine (SLC), a CC chemokine, is expressed in secondary lymphoid organs and mediates the chemotaxis of lymphocytes and DCs via its receptor, CC chemokine receptor 7 (CCR7). By dual-label fluorescence confocal microscopy, we showed MHC class II-positive cells within SLC-staining lymphatic channels in the mouse dermis. SLC was a potent in vitro chemoattractant for cultured, migratory skin DCs, and it enhanced the emigration of MHC class II-positive DCs from mouse skin explants by an average of 2.5-fold. Mature or cytokine-activated, but not resting, Langerhans cells expressed CCR7 mRNA by RT-PCR. Anti-SLC Abs, but not control or anti-eotaxin Abs, blocked the in vivo migration of 51Cr-labeled, skin-derived DCs from footpads to draining LNs by 50% (n = 9, p < 0. 005). Thus, we provide direct evidence that SLC and CCR7 participate in the emigration of DCs from peripheral tissue to LNs via lymphatics.

Animals

Symptomatic hypoglycemia in otherwise healthy, breastfed term newborns.

Transient symptomatic neonatal hypoglycemia, a diagnosis that is made in the neonatal nursery, is not usually associated with apparently normal infants who have been discharged from hospital. We describe 3 such cases that presented at home on day 3 of life with seizures or life-threatening apneas. We postulate that early discharge of apparently normal infants with marginal nutritional or metabolic adaptation, may expose some infants to postdischarge (but still neonatal) hypoglycemia and its attendant risks.

Breast Feeding

Phenylalanine and tyrosine metabolism in neonates receiving parenteral nutrition differing in pattern of amino acids.

Tyrosine is considered to be an indispensable dietary amino acid in the neonate, yet achieving adequate parenteral tyrosine intake is difficult due to its poor solubility. Increasing the supply of phenylalanine is the most common means of compensating for low tyrosine levels. Unfortunately, plasma phenylalanine concentrations are sometimes elevated in infants receiving high phenylalanine intake. This led us to study the phenylalanine and tyrosine metabolism in 16 neonates randomized to receive total parenteral nutrition with either a high or a moderate phenylalanine-containing amino acid solution. A primed, 24-h continuous stable isotope infusion of L-[1-13C]phenylalanine and L-[3,3-2H2]tyrosine was given to enable the measurement of phenylalanine and tyrosine kinetics. Results demonstrated that 1) phenylalanine hydroxylation was significantly greater in infants receiving high phenylalanine, 2) phenylalanine oxidation and percent dose oxidized was also significantly greater in infants receiving high phenylalanine, 3) apparent phenylalanine retention was greater in neonates receiving high phenylalanine, and 4) alternate catabolites of phenylalanine and tyrosine metabolism were significantly greater in infants receiving high phenylalanine compared with moderate phenylalanine. We conclude that neonates respond to increased parenteral phenylalanine intake by increasing their hydroxylation and oxidation rates. The greater oxidation of phenylalanine in infants receiving high phenylalanine in conjunction with the urinary excretion of alternate catabolites of phenylalanine and tyrosine suggests that the high phenylalanine intake may be in excess of needs. However, the lower apparent phenylalanine retention observed in infants receiving moderate phenylalanine suggests that the total aromatic amino acid level of moderate phenylalanine may be deficient for neonatal needs.

Amino Acids

Changes in gastric emptying in early postnatal life.

OBJECTIVE: To study the pattern of gastric emptying in very premature infants and to determine whether there are changes with postnatal age and the ability to tolerate feedings. METHODS: Sequential ultrasound measurements of the gastric antral cross-sectional area were obtained in 32 infants (mean gestational age, 26 +/- 1 weeks) before and after feeding for 2 hours. Studies were carried out after initiation of feedings, when full feedings were received, and at 32 weeks. Infants classified as feeding intolerant (n = 9) were also studied when feedings were restarted. Gastric emptying was assessed by the time taken for antral cross-sectional area to reach maximal value and to decrease to half the maximal increment (half-antral clearance). RESULTS: Delayed antral distention was observed at the time of the initial study in both feeding-tolerant (8 of 23) and feeding-intolerant (8 of 9) infants; however, there were significant differences in times for maximal antral distention (p < 0.002) and half-antral clearance (p < 0.006) between the feeding-tolerant and feeding-intolerant infants. By the time of full feedings, the feeding-intolerant infants showed immediate gastric emptying but still had a longer half-antral clearance time (p < 0.01). By 32 weeks, all infants had immediate antral distention and a more mature curvilinear pattern of gastric emptying. CONCLUSIONS: Knowledge of these different patterns of gastric emptying in very premature infants may lead to the development of more rational feeding strategies.

Aorta, Abdominal

Peripheral chemoreceptors in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) is a rare disorder of unknown etiology, characterized by failure of the autonomic control of respiration. The primary defect is believed to involve central respiratory control; however, no specific lesion has been identified. We report two cases of CCHS (one female, 3 mo of age and one male 2 yr of age) in which there was detailed examination of the neural, muscular, and chemoreceptor components of respiratory control. Although no specific abnormalities were identified in the central nervous system (CNS) or muscles of respiration, striking changes were observed in arterial chemoreceptors, carotid bodies (CB), and airway chemoreceptors, neuroepithelial bodies (NEB). In both cases, CB were small (< 50% of control), with a marked decrease in the number of glomus cells identified by immunostaining for tyrosine hydroxylase and serotonin. Ultrastructural analysis of glomus cells in Case 1 showed a marked decrease in the frequency of dense core vesicles (< 20% of control), the storage site of amine and peptide neurotransmitters. Immunostaining for S100 protein, a marker of sustentacular or Type II cells, was increased up to twofold compared with controls. In the lung, the frequency and size of NEB immunostained for bombesin was increased twofold in both cases, suggesting compensatory hyperplasia of airway chemoreceptors. Since intact peripheral chemoreceptors are essential for respiratory control, especially the response to hypoxia, abnormalities in CB and NEB may contribute to the pathophysiology of CCHS and related conditions such as sudden infant death syndrome (SIDS).

Bombesin

Altered expression of type I collagen, TGF-beta 1, and related genes in rat lung exposed to 85% O2.

The gene expressions of type I collagen and transforming growth factor-beta 1 (TGF-beta 1) were studied in lung tissue of rats exposed to air or 85% O2 for 14 days. Peak expression of type I collagen mRNA was observed by 14 days of 85% O2 exposure, at the same time as maximal immunoreactive type I collagen, which was most marked surrounding the major airways and vessels. TGF-beta 1 mRNA also significantly increased after 14, but not 4 or 6 days of 85% O2 exposure. TGF-beta 1 immunoreactivity was only detected on day 14 of 85% O2 exposure and was localized primarily to the pulmonary epithelium. As an increase in immunoreactive type I collagen was evident by day 6 of O2 exposure, the gene expressions of interstitial collagenase (MMP-1), stromelysin, and the tissue inhibitor of the metalloproteinases (TIMP) were also examined. Increased mRNA expressions of interstitial collagenase and TIMP preceded those of type I collagen and TGF-beta 1, occurring at 4-6 days of exposure to 85% O2, while there was no significant change in stromelysin mRNA. These findings are compatible with the initial O2-mediated increase in type I collagen deposition being a result of an altered proteinase/antiproteinase balance in the lung, and the subsequent more marked deposition being a response to increased TGF-beta 1 synthesis.

Animals

Cutis marmorata telangiectatica congenita.

Cutis marmorata telangiectatica congenita (CMTC) is an uncommon benign condition presenting at birth with levido reticularis, telangiectasia, phlebectasia, and possible ulceration of the involved skin. Diagnosis is made through the clinical picture and supported by characteristic histopathologic changes when present. This condition should not be confused with manifestations of serious system disease and aggressive treatment is not indicated. We describe in this report a case of CMTC.

Child, Preschool

Anatomic, metabolic, neuropsychological, and molecular genetic studies of three pairs of identical twins discordant for dementia of the Alzheimer's type.

Three pairs of twins, each with proved monozygosity, were shown to be discordant for dementia of the Alzheimer's type and to have remained discordant for periods of 8 to 11 years. Dementia of the Alzheimer's type was demonstrated by history; serial clinical examinations; serial measurements of cerebral glucose utilization using positron emission tomography and of cerebral ventricular volumes and of rates of change of volumes using quantitative computed tomography; and by serial neuropsychological tests. The results of each of these measures showed no evidence of clinical abnormality in any unaffected twin. DNA markers from the proximal long arm of chromosome 21 did not distinguish between the affected and the unaffected member of any pair of identical twins. Family pedigrees were negative for Alzheimer's disease. The results suggest that environmental or other nongenetic factors contribute to Alzheimer's disease in discordant monozygotic twins, or that some cases arise by a postzygotic somatic mutation.

Aged

Trot-gallop gait transitions in quadrupeds.

Although the kinematics, mechanics, energetics and mathematics of trot-gallop gait transitions have been discussed in previous papers, no one article has tried to assimilate all the information. This review paper does this and includes a summary of the relatively new engineering (mathematical) approach to analyzing these transitions developed by Schoner et al. (29). The paper also presents unpublished data on gait transitions in cats and monkeys, and attempts to develop some general principles pertaining to trot-gallop transitions. Finally, the paper highlights areas where additional information is needed.

Acceleration

Transforming growth factor alpha: in vivo release by normal human skin following UV irradiation and abrasion.

Transforming growth factor alpha (TGF alpha) is a keratinocyte-growth-stimulating factor which may have a role in epidermal hyperproliferation, psoriasis, and wound healing. Since increased epidermal proliferation occurs in response to UV radiation, we have measured the amount of TGF alpha in exudates from normal and UVB-irradiated human skin. Cutaneous exudates were obtained using the skin chamber abrasion technique from one side of the back of volunteers (n = 10) with normal skin (collected following skin contact times of 2 and 30 min). Exudates were similarly obtained from the contralateral side of the back at sites irradiated 2 h previously with 3 x the minimum erythemal dose UVB. Levels of TGF alpha were measured by radioimmunoassay. Normal human skin released TGF alpha immediately after abrasion: unirradiated, 63 +/- 18 ng/ml; irradiated, 89 +/- 15 ng/ml. Levels of TGF alpha increased within 30 min to 110 +/- 14 ng/ml in unirradiated skin and to 190 +/- 17 ng/ml in irradiated skin. Irradiated sites at 30-min time points were significantly higher (p less than 0.05) than all other samples. The presence of releasable TGF alpha in normal skin suggests a role for TGF alpha in wound repair mechanisms.

Adolescent

Reduced atrial contribution to left ventricular filling in patients with severe tricuspid regurgitation after tricuspid valvulectomy: a Doppler echocardiographic study.

Patients undergoing valvulectomy for isolated tricuspid valve endocarditis offer the unique opportunity to study the effects of acquired right ventricular volume overload on left ventricular filling in persons free of pulmonary hypertension and preexisting left heart disease. Eleven patients who had undergone total or partial removal of the tricuspid valve were compared with 11 age-matched control subjects; Doppler echocardiographic techniques were used to quantify changes in left ventricular filling and to relate them to changes in left ventricular and left atrial geometry caused by right ventricular and right atrial distension. The late diastolic fractional transmitral flow velocity integral, a measure of the left atrial contribution to left ventricular filling, was significantly decreased in patients undergoing tricuspid valvulectomy compared with control subjects (0.22 +/- 0.11 versus 0.32 +/- 0.09; p less than 0.04). Severe tricuspid regurgitation in these patients resulted in marked right atrial distension, reversal of the normal interatrial septal curvature and compression of the left atrium such that left atrial area was significantly smaller than in control subjects (5.9 +/- 2.2 versus 8.6 +/- 1.2 cm2/m2; p less than 0.005). Acting as a receiving chamber, the left ventricle was maximally compressed by the volume-overloaded right ventricle in late diastole, coincident with the timing of atrial systole, resulting in a significant increase in the left ventricular eccentricity index compared with that in control subjects (1.35 +/- 0.14 versus 1.03 +/- 0.1; p less than 0.001). Thus, right ventricular volume overload due to severe tricuspid regurgitation results in left heart geometric alterations that decrease left atrial preload, impair left ventricular receiving chamber characteristics and reduce the atrial contribution to total left ventricular filling.

Adult

Regional cerebral glucose metabolism is normal in young adults with Down syndrome.

Regional CMRglc (rCMRglc) values were measured with [18F]2-fluoro-2-deoxy-D-glucose (18FDG) and positron emission tomography (PET), using a Scanditronix PC-1024-7B scanner, in 14 healthy, noninstitutionalized subjects with trisomy 21 (Down syndrome; DS) (mean age 30.0 years, range 25-38 years) and in 13 sex-matched, healthy volunteers (mean age 29.5 years, range 22-38 years). In the DS group, mean mental age on the Peabody Picture Vocabulary Test was 7.8 years and dementia was not present. Resting rCMRglc was determined with eyes covered and ears occluded in a quiet, darkened room. Global gray CMRglc equaled 8.76 +/- 0.76 mg/100 g/min (mean +/- SD) in the DS group as compared with 8.74 +/- 1.19 mg/100 g/min in the control group (p greater than 0.05). Gray matter regional measurements also did not differ between groups. The ratio of rCMRglc to global CMRglc, calculated to reduce the variance associated with absolute rCMRglc, and right/left ratios did not show any consistent differences. These results show that healthy young DS adults do not have alterations in regional or global brain glucose metabolism, as measured with 18FDG and PET, prior to an age at which the neuropathological changes in Alzheimer disease are reported to occur.

Adult

Determinants of anterior mitral leaflet fluttering in pure aortic regurgitation from pulsed Doppler study of the early diastolic interaction between the regurgitant jet and mitral inflow.

Fluttering of the anterior mitral leaflet may be absent in patients with moderate to severe aortic regurgitation (AR), suggesting that the volumetric severity of AR alone does not determine the presence or absence of abnormal diastolic mitral valve motion. Fifteen patients with moderate to severe AR and normal mitral valves, 9 of whom demonstrated anterior mitral leaflet fluttering, were studied to elucidate the determinants of abnormal anterior mitral leaflet motion in these patients. Pulsed Doppler mapping of the flow-velocity disturbance of AR demonstrated its presence in the third of the left ventricular outflow tract adjacent to the anterior mitral leaflet in 8 of 9 patients with anterior mitral leaflet fluttering and none of the 6 patients without anterior mitral leaflet fluttering (p less than 0.02). The impact of this regurgitant jet on early diastolic transmitral inflow was examined with pulsed Doppler in these 2 groups of patients with AR and in age-matched control subjects. Deceleration of early diastolic transmitral filling was slower in patients with AR and anterior mitral leaflet fluttering than in age-matched control subjects (283 +/- 107 vs 457 +/- 176 cm/s2, p less than 0.02), whereas it was not significantly different from controls in AR patients without anterior mitral leaflet fluttering. This resulted in significant prolongation of the duration of early diastolic transmitral filling in patients with AR and anterior mitral leaflet fluttering (297 +/- 93 vs 203 +/- 44 ms for age-matched control subjects, p less than 0.02), which was not observed in patients with AR who did not have anterior mitral leaflet fluttering.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Brain metabolism as measured with positron emission tomography: serial assessment in a patient with familial Alzheimer's disease.

This paper presents, for the first time, repeated assessments of cerebral metabolism and neuropsychological competence in early Alzheimer's disease. Regional cerebral metabolic rates for glucose were measured with positron emission tomography and 18F-fluoro-2-deoxy-D-glucose on three occasions at 8-month intervals, in a 57-year-old man with Alzheimer's disease of 2 1/2 years' duration and with a family history of neuropathologically confirmed Alzheimer's disease. Data were compared with mean cerebral metabolic rates from 12 healthy men. No differences in regional cerebral metabolic rates for glucose were found on the initial patient scan, whereas metabolism on the second and third scans was reduced significantly in the parietal lobes and bilaterally in some parietal lobe regions. Memory loss was demonstrable at the first scan, but then and at later scans, other aspects of cognitive performance remained within normal limits (Wechsler Adult Intelligence Scale, Boston Naming Test, Two-dimensional Block Construction). The results show that memory loss can precede a measurable reduction of cerebral metabolism in early Alzheimer's disease, but that later reductions in parietal lobe metabolism may not be accompanied by additional measurable neuropsychological deficits.

Aged

Cerebral glucose utilization, as measured with positron emission tomography in 21 resting healthy men between the ages of 21 and 83 years.

Positron emission tomography (PET) scanning with 18F-2-deoxy-D-glucose was employed to examine hemispheric and regional rates of cerebral glucose utilization in 21 resting healthy men between the ages of 21 and 83 years. The eyes of the subjects were covered and the external auditory canals were plugged with cotton in the 45 minutes following injection of tracer. Mean hemispheric cerebral metabolic rates for glucose (CMRglc) averaged 4.3 to 4.4 mg x 100 g-1 X min-1, and mean hemispheric grey matter glucose utilization, (CMRglc)grey, averaged 5.2 to 5.3 mg x 100 g-1 X min-1. Neither parameter was correlated significantly with age, nor were their right/left ratios correlated with age (P greater than 0.05). The mean ratios, furthermore, did not differ significantly from 1. Regional cerebral metabolic rates for glucose, rCMRglc, at each of 31 identified midline and bilateral structures also were not correlated significantly with age. Mean rCMRglc ranged from 2.6 mg X 100 g-1 X min-1 at the centrum semiovale to 6.2 mg . 100 g-1 X min-1 at the precentral gyrus of the frontal lobe and precuneus of the parietal lobe. The results indicate that the cerebral metabolic rate for glucose is not correlated with age in healthy men.

Adult