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Biomedical subjects

R Locke

Publications and source records attributed to R Locke.

At least 19 recordsLinked to original sources
PubMed2001

Immaturity or starvation? Longitudinal study of leptin levels in premature infants.

OBJECTIVE: Leptin, the protein product of the ob gene, is a potential placental growth factor and is integral to the body's system of energy regulation as shown in animal models. Premature infants are especially vulnerable to changes in energy regulation, and several studies have demonstrated a rapid fall in leptin values at birth. The purpose of the present investigation was to measure leptin levels in premature infants throughout hospitalization. METHODS: Eligible infants were less than 32 weeks' gestation, appropriate for gestational age, and hospitalized at Christiana Hospital Special Care Nursery. Serum samples for leptin analysis were drawn within 24 h of birth and twice a week thereafter until discharge. Concurrent growth measurements were obtained with each leptin sample. Body mass index, ponderal index, and midarm circumference/head circumference ratios were calculated to assess growth. RESULTS: Leptin levels were low and remained low for the duration of the premature infants' hospitalization (mean +/- SD = 1.35 +/- 0.63 ng/ml/ml, range 0-3.06). After controlling for weight, there was a small (r(2) = 0.1, p < 0.00001) but significant correlation between leptin and postnatal age after 4 days of age. Despite an increase in caloric intake during the study period, there was no relationship between leptin and caloric intake. There were significant negative correlations between measurements of growth and both leptin and the leptin/weight ratio. Maternal diabetes and the use of steroids had small but significant effects on the leptin/weight ratio. CONCLUSION: In this population of predominantly female premature infants, leptin levels were very low as compared to term infants, children and adults, and did not change appreciably over the study period. The low leptin levels seen in these premature infants are similar to those levels seen in malnourished adults, anorexics, and in animal models of starvation. We speculate that a critical adipose store needs to be reached before increased amounts of leptin can be adequately produced. Persistently low leptin levels may also reflect an immaturity in the hypothalamic-pituitary-adrenal axis.

Aging↗
PubMed2001

Leptin levels in preterm human breast milk and infant formula.

OBJECTIVE: Leptin, a hormone present in breast milk, is involved in energy regulation and metabolism. The purpose of this investigation was to determine whether leptin is present in either preterm breast milk (PBM) or preterm formula (PF). The effects of delivery methods and pasteurization on leptin levels also were evaluated. METHODS: PBM samples were obtained from 29 mothers who delivered infants at between 23 and 34 weeks' gestation. Leptin levels were measured in PBM and PF with the use of a radioimmunoassay specific for human and bovine leptin, respectively. Milk samples were pasteurized by fast- and slow-heating methods. PBM and PF spiked with human leptin were delivered through catheters by bolus and continuous administration to determine the effects of delivery method on recoverable leptin levels. RESULTS: Median PBM leptin concentration was 5.28 ng/mL (intraquartile range: 24.79). Birth gestational age, birth weight, and gender of the infant did not significantly influence PBM leptin levels. Neither bolus nor continuous feeding practices affected leptin levels in PBM or spiked PF. However, pasteurization significantly reduced the amount of detectable leptin in PBM. CONCLUSIONS: PBM leptin levels were highly variable and similar to levels reported for term breast milk. There was no effect of postnatal age on PBM leptin concentrations. Sterilization decreased detectable leptin levels, whereas feeding practices had no adverse effect on the quantity of leptin delivered. Although no infant formula contained leptin, leptin could be added to formula and delivered through various feeding methods without loss.

Blotting, Western↗
PubMed2000

Mammalian Notch1 is modified with two unusual forms of O-linked glycosylation found on epidermal growth factor-like modules.

Notch is a large cell-surface receptor known to be an essential player in a wide variety of developmental cascades. Here we show that Notch1 endogenously expressed in Chinese hamster ovary cells is modified with O-linked fucose and O-linked glucose saccharides, two unusual forms of O-linked glycosylation found on epidermal growth factor-like (EGF) modules. Interestingly, both modifications occur as monosaccharide and oligosaccharide species. Through exoglycosidase digestions we determined that the O-linked fucose oligosaccharide is a tetrasaccharide with a structure identical to that found on human clotting factor IX: Sia-alpha2,3-Gal-beta1, 4-GlcNAc-beta1,3-Fuc-alpha1-O-Ser/Thr. The elongated form of O-linked glucose appears to be a trisaccharide. Notch1 is the first membrane-associated protein identified with either O-linked fucose or O-linked glucose modifications. It also represents the second protein discovered with an elongated form of O-linked fucose. The sites of glycosylation, which fall within the multiple EGF modules of Notch, are highly conserved across species and within Notch homologs. Since Notch is known to interact with its ligands through subsets of EGF modules, these results suggest that the O-linked carbohydrate modifications of these modules may influence receptor-ligand interactions.

Animals↗
PubMed1999

Miniature EPSPs and sensory encoding in the primary afferents of the vestibular lagena of the toadfish, Opsanus tau.

The synaptic activity transmitted from vestibular hair cells of the lagena to primary afferent neurons was recorded in vitro using sharp, intracellular microelectrodes. At rest, the activity was composed of miniature excitatory postsynaptic potentials (mEPSPs) at frequencies from 5 to 20/s and action potentials (APs) at frequencies betwen 0 and 10/s. mEPSPs recorded from a single fiber displayed a large variability. For mEPSPs not triggering APs, amplitudes exhibited an average coefficient of variance (CV) of 0.323 and rise times an average CV of 0.516. APs were only triggered by mEPSPs with larger amplitudes (estimated 4-6 mV) and/or steeper maximum rate of rise (10.9 mV/ms, +/- 3.7 SD, n=4 experiments) compared to (3.50 mV/ms, +/-0.07 SD, n=6 experiments) for nontriggering mEPSPs. The smallest mEPSPs showed a fast rise time (0.99 ms between 10% and 90% of peak amplitude) and limited variability across fibers (CV:0.18) confirming that they were not attenuated signals, but rather represented single-transmitter discharges (TDs). The mEPSP amplitude and rise-time relationship suggests that many mEPSPs represented several, rather than a single pulse of secretion of TDs. According to the estimated overall TD frequency, the coincidence of TDs contributing to the same mEPSP were not statistically independent, indicating a positive interaction between TDs that is reminiscent of the way subminiature signals group to form miniature signals at the neuromuscular junction. Depending on the duration and intensity of efferent stimulation, a complete block of AP initiation occurred either immediately or after a delay of a few seconds. Efferent stimulation did not significantly change AP threshold level, but abruptly decreased mEPSP frequency to a near-complete block that followed the block of APs. Maximum mEPSP rate of rise decreased during, and recovered progressively after, efferent stimulation. After termination of efferent stimulation, mEPSP amplitude did not recover instantly and for a few seconds the amplitude distribution of synaptic events showed fewer large-amplitude events than during the control period. This confirms that mEPSP amplitude and rate of rise properties, which are critical for triggering afferent APs, are modified by efferent activity. The depression of afferent AP firing during efferent stimulation corresponded to a decrease in mEPSP frequency and, to a lesser extent, a decrease in mEPSP amplitude and rate of rise, suggesting, a decrease in the level of interaction among TDs contibuting to a mEPSP.

Action Potentials↗
PubMed1997

Effect of maternal depression on premature infant health during initial hospitalization.

This study evaluates the effect of maternal depression on neonatal health status in premature infants during their initial hospitalization. Infants younger than 34 weeks' gestation born to nondrug abusing mothers were enrolled in the study. Thirty-one mother-infant pairs were identified. Maternal depression was evaluated by the Center for Epidemiologic Studies-Depression Scale (CES-D). Scores > or = 16 defined maternal depression. Initial infant physiologic health status was determined by the Score for Neonatal Acute Physiology (SNAP). In-hospital health status was assessed by the following variables: days receiving supplemental oxygen, days on mechanical ventilation (VENT), and days not on enteral feeding (NPO). Health status variables evaluated for long-term outcome included bronchopulmonary dysplasia at 28 days (BPD), BPD at 34 weeks' postmenstrual age (BPD-34), and intraventricular hemorrhage (IVH). Seventeen (55%) of 31 mothers manifested depression on the CES-D. No epidemiologic differences were found between this group and the nondepressed mothers. No differences in gestation or birth weight was detected between the preterm infants of depressed versus nondepressed mothers. The CES-D scores correlated significantly with SNAP (r = .36, P < .02). Infants of depressed mothers experienced significantly worse outcomes in the occurrence of BPD (P = .015), BPD-34 (P = .049), and IVH (P = .055). This study confirms that maternal depression occurs frequently in mothers of preterm infants and adversely affects the presenting neonatal health status of their babies during the initial hospitalization. Maternal depression was related to the severity of the initial neonatal illness and was significantly related to IVH and BPD. These factors may have long-term consequences for subsequent growth, neurodevelopment, and recurrence of related health problems.

Bronchopulmonary Dysplasia↗
PubMed1997

The Dundee out-of-hours cooperative: preliminary outcomes for the first year of operation.

The Dundee out-of-hours cooperative (DDOC) was the first of its kind to be developed in a city in Scotland. In its first year of operation, the key features of the cooperative were that (a) two doctors could deal with the large majority of out-of-hours calls for a population of just under 100,000 patients, (b) only one third of calls required a home visit, (c) most calls were handled within a period of time acceptable to patients, (d) seven out of 10 patients rated the service equal to or better than previous services, and (e) there were extended opportunities for general practitioners (GPs) involved in the scheme to meet with other colleagues during out-of-hours work.

Family Practice↗
PubMed1991

Effect of nasal CPAP on thoracoabdominal motion in neonates with respiratory insufficiency.

Thoracoabdominal motion (TAM) profiles were determined in ten infants requiring nasal continuous positive airway pressure (CPAP) and supplemental oxygen, in order to assess the influence of CPAP on chest wall function in infants with respiratory insufficiency. (TAM) was quantitated by respiratory inductive plethysmography, measuring relative motion of the rib cage and abdomen. Baseline pulmonary function (without CPAP support) was assessed from simultaneous measurements of transpulmonary pressure, air flow, and tidal volume. Measurements of (TAM) were acquired at baseline and at nasal CPAP levels of 0, 3, 5, and 8 cm H2O, in randomized order. Without CPAP, relative paradoxical motion occurred, i.e., the rib cage collapsed inward instead of expanding outward early in inspiration. With CPAP, TAM resembled the pattern in preterm infants, without lung disease. We found that nasal CPAP lowers the phase angle in infants with respiratory insufficiency (P less than 0.003), indicating improved synchrony of TAM. In addition, the improvement with nasal CPAP was related to the severity of pulmonary compromise at baseline. We speculate that changes in TAM associated with nasal CPAP arise from an interaction between pulmonary mechanics and an enhanced stability of the chest wall. In this context, the greater synchrony of TAM is suggestive of an improved breathing strategy. This may be a noninvasively obtainable marker of an effective nasal CPAP level in infants with altered pulmonary and chest wall mechanics.

Humans↗
PubMed1985

Hypersensitive prostaglandin and thromboxane response to hormones in rabbit colitis.

Inflammation of the colon is associated with increased production of prostaglandins (PG) and thromboxanes (Tx), and these eicosanoids may contribute to the inflammatory, secretory, and motility dysfunctions in colitis. To evaluate the potential role of peptide hormones in the enhanced eicosanoid release, colitis was established in rabbits by a delayed-type hypersensitivity reaction to dinitrochlorobenzene and by an immune-complex-mediated reaction. PG and Tx were identified in the venous effluent of isolated perfused colons by radiochromatography after [14C]arachidonic acid prelabeling, as well as by bioassay, and then quantitated by immunoassay. The two colitis models were morphologically similar. Basal release of PGE2, PGI2, and TxA2 was two- to threefold greater from colitis tissue than from control tissue. Bradykinin (BK) and angiotensin II (ANG II) increased release of 14C-labeled eicosanoids, whereas several gastrointestinal hormones had no effect. In control colons, BK and ANG II increased PGE2 and PGI2 release (by about 2-fold) but did not alter TxA2. In contrast, BK and ANG II markedly exaggerated the release of eicosanoids in colitis. BK increased TxA2 release with 10-ng bolus injections in colitis, but there was no response with up to 10-micrograms bolus injections in control colons. The BK-induced Tx release in colitis was associated with an increase in vascular resistance (measured as perfusion pressure). Infusion of the selective Tx inhibitors dazoxiben and OKY-046 reduced TxB2 release by 96% and blunted the transient rise in perfusion pressure (from 17 +/- 5 to 5 +/- 2 mmHg). Since BK and possibly ANG II are increased at sites of inflammation, the hypersensitive eicosanoid response to these peptides may augment the eicosanoid-mediated manifestations of colitis.

Animals↗
PubMed1984

The use of surface oximetry to assess bowel viability.

Tissue depends on perfusion, but tissue oxygenation measurements have been impractical. To develop a method for the clinical evaluation of bowel viability, we studied PO2 on the bowel surface (PSO2). The PSO2 was assessed on the stomach and intestine of 11 dogs. Normal small-bowel PSO2 was 44 +/- 11 mm Hg (mean +/- SD). When bowel vasculature was interrupted PSO2 rapidly decreased. Reductions in PSO2 were related to the degree of ischemia produced. Anastomoses were performed on partially devascularized bowel to determine anastomotic viability at various levels of PSO2. The PSO2 measured just prior to anastomosis predicted viability of the anastomoses at 48 hours. Anastomoses below 30% of predevascularization PSO2 necrosed. Between 30% and 50%, one third of anastomoses leaked. At PSO2 values above 50% of initial normal value all anastomoses healed. Surface oximetry allows accurate intraoperative assessment of bowel perfusion.

Animals↗
PubMed1983

Human muscle: a model for the study of human neoplasia.

Human muscle (HM) was used in an organ culture system to study the growth of human tumor cells and to test an antitumor drug. The HM system mimicked the in vivo situation regarding the behavior of neoplastic versus normal cells in that tumor cells proliferated extensively and invaded, while normal cells showed only a limited proliferative potential and a limited invasion was observed with fibroblasts but not with epithelial cells. In addition, when human plasma (HP) was used in place of fetal bovine serum (FBS) and cell culture medium as a source of nutrients, the tumor cells displayed a more aggressive histopathologic pattern. The HM system, as illustrated by the 5-FU results, allows the direct visualization of the effect to an antitumor agent not only on tumor cell growth but also on a range of histopathologically evaluable characteristics of the interaction of tumor cells with the host tissue. The HM system provides for the first time an in vitro experimental model using easily accessible adult human tissue to study cancer and its treatment.

Cell Division↗
PubMed1982

Risk assessment in a federal regulatory agency: an assessment of risk associated with the human consumption of some species of fish contaminated with polychlorinated biphenyls (PCBs).

The problem of polychlorinated biphenyls (PCBs) became a national concern in 1971 when several accidental contaminations of foods were reported. Extensive efforts were undertaken by FDA to reduce the residues of PCBs in food. However, the PCB levels in several species of fresh-water fish have raised concern about the PCB residues from environmental contamination, and it is this concern which has prompted a reassessment of the human risk involved from consumption of such fish. The human epidemiology and animal toxicity of PCB exposure are reviewed, as well as risk assessment in general. Specific examples to risk assessment involving extrapolation of animal data to humans, based on several levels of human exposure to PCBs in fish, are presented.

Animals↗