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Biomedical subjects

T Cronin

Publications and source records attributed to T Cronin.

17 recordsLinked to original sources

Should children with developmental and behavioural problems be routinely screened for lead?

AIM: To test the hypothesis that children with behavioural and/or developmental problems have significantly higher blood lead concentrations than the general childhood population. METHODS: Blood samples were taken from 69 children with behavioural and/or developmental problems and 136 controls (children admitted for elective day case surgery under general anaesthetic). Blood lead estimations were carried out using graphite furnace atomic absorption RESULTS: Children with behavioural and/or developmental problems had higher lead concentrations than controls, both in terms of their distribution across the group (mean(geometric) lead concentrations: 40.7 (cases), 29.2 (controls), ratio of the means(geometric) 1.35 (95% CI 1.17, 1.58)) and the proportion of children with lead concentrations above those commonly defined as "toxic"-that is, 100 microg/l (12% (cases), 0.7% (controls); p < 0.001). Multiple linear regression suggested that this difference was not explained by differences in age, sex, or socioeconomic status of the two comparison groups. CONCLUSIONS: Children with behavioural and/or developmental problems are more likely to have significantly higher blood lead concentrations than the general childhood population. Lead, a known and more importantly, a treatable neurotoxin, would further contribute to the impairment suffered by these children. We argue that this group of children should be routinely screened for lead.

Case-Control Studies↗

Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains.

Lipid second messengers generated by phosphoinositide (PI) 3-kinases regulate diverse cellular functions through interaction with pleckstrin homology (PH) domains in modular signaling proteins. The PH domain of Grp1, a PI 3-kinase-activated exchange factor for Arf GTPases, selectively binds phosphatidylinositol 3,4,5-trisphosphate with high affinity. We have determined the structure of the Grp1 PH domain in the unliganded form and bound to inositol 1,3,4,5-tetraphosphate. A novel mode of phosphoinositide recognition involving a 20-residue insertion within the beta6/beta7 loop explains the unusually high specificity of the Grp1 PH domain and the promiscuous 3-phosphoinositide binding typical of several PH domains including that of protein kinase B. When compared to other PH domains, general determinants of 3-phosphoinositide recognition and specificity can be deduced.

Amino Acid Sequence↗

Concentrations of trace minerals in the spinal cord of horses with equine motor neuron disease.

OBJECTIVE: To compare concentrations of trace minerals in the spinal cord of horses with equine motor neuron disease (EMND) with those of horses without neurologic disease (control horses). ANIMALS: 24 horses with EMND and 22 control horses. PROCEDURE: Spinal cord trace mineral concentrations in horses with EMND and control horses were analyzed by use of inductively coupled plasma atomic emission spectroscopy (calcium, phosphorus, sodium, potassium, magnesium, copper, iron, manganese, nickel, zinc, aluminum, cobalt, and chromium), atomic absorption spectrophotometry (lead and cadmium), flameless atomic absorption (mercury), and fluorometry (selenium). RESULTS: Copper concentration was significantly higher in the spinal cord of horses with EMND, compared with control horses; spinal cord concentrations of all other trace minerals were similar between groups. CONCLUSION AND CLINICAL RELEVANCE: Among spinal cord trace minerals investigated in the study, only copper concentrations were significantly different between horses with EMND and horses without neurologic disease, which suggests that copper may be involved in the pathogenesis of EMND. An hypothesis of oxidative injury in this disease is supported by the finding of increased copper concentrations in the spinal cord and by low vitamin E concentrations reported by other researchers.

Aluminum↗

Changing patterns of care for occult breast lesions in a community teaching hospital.

We performed a retrospective analysis of 384 consecutive stereotactic breast biopsies (SBBs) from March 1995 through January 1999 and compared it with our historical breast biopsy experience. Two hundred forty-four patients underwent biopsies for microcalcifications and 135 patients for abnormal mammographic densities. Pathology diagnoses included 302 patients with benign disease, 35 patients with atypical ductal hyperplasia, 4 patients with lobular carcinoma in situ, 29 patients with ductal carcinoma in situ, and 9 patients with invasive breast cancer. These diagnostic rates were compared with our prior needle-localized pathology findings. For the study period, the number of mammograms, open biopsies, and needle-localized biopsies remained stable. The number of SBBs, however, increased progressively in every year. Medicare reimbursement for SBB was $921.19, and for breast biopsy after needle localization, $1566.22. Our study strongly suggests that the availability of SBB has significantly lowered the threshold for recommending biopsy of abnormal mammograms. The increased utilization of SBB almost certainly indicates an increase in the overall cost of breast care. This cost must be balanced against substantial potential benefits of this minimally invasive technique: possible earlier diagnosis of atypical and precancerous lesions, patient reassurance in cases of uncertain mammographic interpretation, and a reduced need for follow-up of indeterminate mammograms.

Adult↗

Visual mate choice in poison frogs.

We investigated female mate choice on the basis of visual cues in two populations of Dendrobates pumilio, the strawberry poison frog, from the Bocas del Toro Archipelago in Panama, Central America. Mate choice experiments were carried out by presenting subject females of each of two morphs of this species (orange and green) from two different island populations (Nancy Key and Pope Island) with object frogs (one of each morph) under glass at one end of a terrarium. Recorded calls were played simultaneously from behind both object frogs. The experiments were carried out under two light regimes: (i) white light, and (ii) relatively monochromatic filtered blue light. Subject females from each population displayed a significant preference for their own morph under white light, but not under blue light. These results indicate that female D. pumilio use visual cues in mate choice, and suggest that colour may be the visual cue they use.

Animals↗

bcl-2 prolongs neuronal survival during hypoxia-induced apoptosis.

In vivo models of hypoxic-ischemic brain injury have shown altered expression of a number of genes that are important in regulating neuronal survival. However, it is not clear as to whether hypoxia alone can alter the expression of genes regulating neuronal survival. We hypothesized that (1) hypoxia alone alters the expression of bcl-2 in neurons, (2) the severity and duration of hypoxia influence bcl-2 expression, and (3) the alteration of bcl-2 expression has an important role in regulating neuronal survival during hypoxia. Embryonic rat neocortical neurons cultured for 7-10 days were exposed to 0.1, 1, or 3% oxygen for various durations and were removed for analyses at 24-h intervals. Under all hypoxic conditions, neurons exhibited morphologic changes, as assessed by electron microscopy and Annexin V staining, consistent with apoptosis. Immunoblot and immunofluorescence analyses revealed an increase in neuronal bcl-2 protein during hypoxic exposure. Quantitative immunofluorescence analyses of bcl-2 immunostained neurons indicated that expression of bcl-2 was altered by the duration and severity of hypoxia. Attenuation of bcl-2 expression by antisense oligonucleotides decreased the proportion of surviving neurons by approximately 50% after 48 h of exposure to 0.1% oxygen. We conclude that observed increase in bcl-2, in part, plays an important role in neuronal survival during exposure to hypoxia.

Animals↗

Perception of postural limits in elderly nursing home and day care participants.

This study explored whether, when compared to young community-dwelling individuals, elderly nursing home and day care participants have less accurate perceptions of their postural stability borders (postural limits). Subjects estimated their performance before executing maximum forward reaches while maintaining the feet stationary. Whereas young subjects tended to underestimate their reaching limits, elderly subjects displayed no significant difference between estimated and actual values. Furthermore, errors in estimated reach limits associated with reaching ability, with less-able reachers tending to more greatly overestimate their abilities. This suggests that elderly nursing home and day care participants, and especially those with impaired postural limits, lack the potential "safety factor" observed in young subjects of underestimating their stability borders. Therefore, the link between decreased postural limits and falls in older persons may in part be due to lack of awareness of such declines, and the resulting tendency to plan movements which create loss of balance.

Accidental Falls↗

Redundant proteolytic activation of a viral superantigen.

Proteolytic activation of viral superantigens (vSAgs)4 expressed in Chinese hamster ovary (CHO) cells is required for T cell stimulation, and is mediated primarily by the protein convertase (PC) furin. Three PC recognition sites are highly conserved in vSAgs, but it was not known which sites are required for PC dependent vSAg activation. Moreover, because the PC recognition sites are not conserved in all functional vSAgs it was possible that activation could occur by processing at any of several sites. To identify the location(s) where processing of vSAg7 generates an active superantigen, each of two PC recognition sites, and a third related site were altered by in vitro mutagenesis, and the mutant proteins were tested for their abilities to activate T cells. Mutation of the PC recognition site at position 68-71 in vSAg7 had no effect on its ability to activate T cells. Mutation of the processing site at position 169-172 completely abolished T cell activation, and indicated that cleavage at this position was obligatory for proteolytic activation of vSAg7. However, introduction of a PC recognition site at position 192-195, a position that in many other vSAgs encodes a PC recognition site, restored activity to a vSAg7 protein that lacked a recognition site at position 169-172. The data revealed that processing of vSAgs at either position 169-172 or 192-195 was sufficient for vSAg7 activation, and explain how vSAgs that lack some PC recognition sites can be activated by proteolytic processing.

Animals↗

Self-association of spectrin's repeating segments.

We have examined the self-association behavior in solution of one of the repeating conformational segments of Drosophila spectrin, D-alpha-14, as well as of the two-segment unit, D-alpha-14,15. In both polypeptides, sedimentation equilibrium and nondenaturing gel electrophoresis detect a reversible, moderate affinity (K2 approximately equal to 10(4) M-1) dimerization reaction. Equilibration between monomer and dimer is kinetically limited near 5 degrees C, but occurs at a measurable rate at temperatures > or = 20 degrees C. The temperature dependence for equilibration is consistent with the requirement for extensive disruption of helix-helix packing as the reaction proceeds in either direction. Hydrodynamic studies by means of sedimentation velocity confirm that in solution the C helix in the monomer of D-alpha_14 is folded back to interact with the A and B helices, and that the form of monomeric subunit observed in the crystal structure, in which the A and B helices are continuous, does not persist in the monomer in solution. Both the dimer of D-alpha-14 and the monomer of D-alpha-14,15 appear to be twice the length of the D-alpha-14 monomer, while the frictional ration of the D-alpha-14,15 dimer is consistent with four end-to-end triple alpha-helical domains.

Animals↗

Polarization vision in cuttlefish in a concealed communication channel?

Polarization sensitivity is well documented in marine animals, but its function is not yet well understood. Of the cephalopods, squid and octopus are known to be sensitive to the orientation of polarization of incoming light. This sensitivity arises from the orthogonal orientation of neighboring photoreceptors. Electron microscopical examination of the retina of the cuttlefish Sepia officinalis L. revealed the same orthogonal structure, suggesting that cuttlefish are also sensitive to linearly polarized light. Viewing cuttlefish through an imaging polarized light analyzer revealed a prominent polarization pattern on the arms, around the eyes and on the forehead of the animals. The polarization pattern disappeared when individuals lay camouflaged on the bottom and also during extreme aggression display, attacks on prey, copulation and egg-laying behavior in females. In behavioral experiments, the responses of cuttlefish to their images reflected from a mirror changed when the polarization patterns of the reflected images were distorted. These results suggest that cuttlefish use polarization vision and display for intraspecific recognition and communication.

Journal Article↗

Medium term functional results of single-lung transplantation for endstage obstructive lung disease.

Controversy has surrounded the use of single-lung transplantation (SLT) for the treatment of endstage obstructive lung disease. In recent years, several transplant centers have performed SLT for such indications. In this report, we describe functional results in patients undergoing SLT for obstructive lung disease, twenty-two followed over one year and 10 over two years. Data include pulmonary function testing, gas exchange, quantitative ventilation and perfusion to the lung graft, and results of symptom-limited graded cycle exercise testing after SLT. Our results show improvement in obstructive dysfunction FEV1 0.49 +/- 0.13 L (16 +/- 4% predicted) pre-SLT to 1.71 +/- 0.43 L (57 +/- 12% predicted) 3 mo after SLT, FEV1/FVC 0.30 +/- 0.07 pre-SLT to 0.75 +/- 0.09 3 mo after SLT, and improvement in arterial oxygenation, PaO2 58 +/- 10 mm Hg pre SLT to PaO2 86 +/- 13 mm Hg 3 mo post-SLT. In addition, these improvements were sustained up to 1 to 2 yr post-SLT. The majority of ventilation and perfusion go to the new lung graft. After SLT, patients have reduced maximum oxygen consumption (VO2max 40 to 60% predicted) but do not have ventilatory limitation to exercise and can carry out daily activities without compromise. We conclude that SLT is a viable medium-term therapeutic option for endstage obstructive lung disease. The long-term future of this technique remains to be determined.

Adult↗

Crystal structure of the repetitive segments of spectrin.

The elongated proteins of the spectrin family (dystrophin, alpha-actinin, and spectrin) contain tandemly repeated segments and form resilient cellular meshworks by cross-linking actin filaments. The structure of one of the repetitive segments of alpha-spectrin was determined at a 1.8 angstrom resolution. A segment consists of a three-helix bundle. A model of the interface between two tandem segments suggests that hydrophobic interactions between segments may constrain intersegment flexibility. The helix side chain interactions explain how mutations that are known to produce hemolytic anemias disrupt spectrin associations that sustain the integrity of the erythrocyte membrane.

Amino Acid Sequence↗

Advance directives for HIV-positive patients.

The authors surveyed HIV-positive patients to determine their knowledge of and interest in advance directives and their preferences for end-of-life care. The results of this study make clear the need to institute a program of education for those desiring to know more about advance directives.

Adult↗

Single lung transplantation for primary pulmonary hypertension.

Single lung transplantation has become a therapeutic option for end-stage interstitial lung disease and obstructive lung disease. Our group recently extended this treatment to three patients with primary pulmonary hypertension. All patients had marked decreases in pulmonary artery pressures and pulmonary vascular resistance and increases in cardiac output following single lung transplantation. Spirometry, lung volumes, and diffusion capacity were not different in comparison to preoperative studies. Quantitative ventilation-perfusion scans revealed the majority of perfusion distributed to the transplanted lung, with ventilation approximately equally divided between the native and the transplanted lung. Despite ventilation-perfusion imbalance, there was no resting hypoxemia and there was no arterial oxygen desaturation with exercise. One patient expired on the 30th postoperative day due to cytomegalovirus infection of the lungs. In the remaining two patients, maximum exercise capacity following transplantation was near normal in one recipient and reduced in the second recipient. Of note, there was no evidence of ventilatory limitation or impaired oxygenation during exercise in these two recipients. Although an exaggerated exercise ventilatory response was present, this did not limit exercise performance. This report supports the use of single lung transplantation for the treatment of primary pulmonary hypertension.

Adult↗