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G Egan

Publications and source records attributed to G Egan.

14 recordsLinked to original sources
PubMed2001

Neuroimaging of cerebral activations and deactivations associated with hypercapnia and hunger for air.

There are defined medullary, mesencephalic, hypothalamic, and thalamic functions in regulation of respiration, but knowledge of cortical control and the elements subserving the consciousness of breathlessness and air hunger is limited. In nine young adults, air hunger was produced acutely by CO(2) inhalation. Comparisons were made with inhalation of a N(2)/O(2) gas mixture with the same apparatus, and also with paced breathing, and with eyes closed rest. A network of activations in pons, midbrain (mesencephalic tegmentum, parabrachial nucleus, and periaqueductal gray), hypothalamus, limbic and paralimbic areas (amygdala and periamygdalar region) cingulate, parahippocampal and fusiform gyrus, and anterior insula were seen along with caudate nuclei and pulvinar activations. Strong deactivations were seen in dorsal cingulate, posterior cingulate, and prefrontal cortex. The striking response of limbic and paralimbic regions points to these structures having a singular role in the affective sequelae entrained by disturbance of basic respiratory control whereby a process of which we are normally unaware becomes a salient element of consciousness. These activations and deactivations include phylogenetically ancient areas of allocortex and transitional cortex that together with the amygdalar/periamygdalar region may subserve functions of emotional representation and regulation of breathing.

Adult↗
PubMed2001

Brain responses associated with consciousness of breathlessness (air hunger).

Little is known about the physiological mechanisms subserving the experience of air hunger and the affective control of breathing in humans. Acute hunger for air after inhalation of CO(2) was studied in nine healthy volunteers with positron emission tomography. Subjective breathlessness was manipulated while end-tidal CO(2-) was held constant. Subjects experienced a significantly greater sense of air hunger breathing through a face mask than through a mouthpiece. The statistical contrast between the two conditions delineated a distributed network of primarily limbic/paralimbic brain regions, including multiple foci in dorsal anterior and middle cingulate gyrus, insula/claustrum, amygdala/periamygdala, lingual and middle temporal gyrus, hypothalamus, pulvinar, and midbrain. This pattern of activations was confirmed by a correlational analysis with breathlessness ratings. The commonality of regions of mesencephalon, diencephalon and limbic/paralimbic areas involved in primal emotions engendered by the basic vegetative systems including hunger for air, thirst, hunger, pain, micturition, and sleep, is discussed with particular reference to the cingulate gyrus. A theory that the phylogenetic origin of consciousness came from primal emotions engendered by immediate threat to the existence of the organism is discussed along with an alternative hypothesis by Edelman that primary awareness emerged with processes of ongoing perceptual categorization giving rise to a scene [Edelman, G. M. (1992) Bright Air, Brilliant Fire (Penguin, London)].

Adult↗
PubMed2001

Neuroimaging evidence implicating cerebellum in the experience of hypercapnia and hunger for air.

Recent neuroimaging and neurological data implicate cerebellum in nonmotor sensory, cognitive, vegetative, and affective functions. The present study assessed cerebellar responses when the urge to breathe is stimulated by inhaled CO(2). Ventilation changes follow arterial blood partial pressure CO(2) changes sensed by the medullary ventral respiratory group (VRG) and hypothalamus, entraining changes in midbrain, pons, thalamus, limbic, paralimbic, and insular regions. Nearly all these areas are known to connect anatomically with the cerebellum. Using positron emission tomography, we measured regional brain blood flow during acute CO(2)-induced breathlessness in humans. Separable physiological and subjective effects (air hunger) were assessed by comparisons with various respiratory control conditions. The conjoint physiological effects of hypercapnia and the consequent air hunger produced strong bilateral, near-midline activations of the cerebellum in anterior quadrangular, central, and lingula lobules, and in many areas of posterior quadrangular, tonsil, biventer, declive, and inferior semilunar lobules. The primal emotion of air hunger, dissociated from hypercapnia, activated midline regions of the central lobule. The distributed activity across the cerebellum is similar to that for thirst, hunger, and their satiation. Four possible interpretations of cerebellar function(s) here are that: it subserves implicit intentions to access air; it provides predictive internal models about the consequences of CO(2) inhalation; it modulates emotional responses; and that while some cerebellar regions monitor sensory acquisition in the VRG (CO(2) concentration), others influence VRG to adjust respiratory rate to optimize partial pressure CO(2), and others still monitor and optimize the acquisition of other sensory data in service of air hunger aroused vigilance.

Adult↗
PubMed2000

Neuroimaging evidence implicating cerebellum in support of sensory/cognitive processes associated with thirst.

Recent studies implicate the cerebellum, long considered strictly a motor control structure, in cognitive, sensory, and affective phenomenon. The cerebellum, a phylogenetically ancient structure, has reciprocal ancient connections to the hypothalamus, a structure important in vegetative functions. The present study investigated whether the cerebellum was involved in vegetative functions and the primal emotions engendered by them. Using positron emission tomography, we examined the effects on the cerebellum of the rise of plasma sodium concentration and the emergence of thirst in 10 healthy adults. The correlation of regional cerebral blood flow with subjects' ratings of thirst showed major activation in the vermal central lobule. During the development of thirst, the anterior and posterior quadrangular lobule, lingula, and the vermis were activated. At maximum thirst and then during irrigation of the mouth with water to alleviate dryness, the cerebellum was less activated. However, 3 min after drinking to satiation, the anterior quadrangular lobule and posterior cerebellum were highly activated. The increased cerebellar activity was not related to motor behavior as this did not occur. Instead, responses in ancient cerebellar regions (vermis, fastigal nucleus, archicerebellum) may be more directly related to vegetative and affective aspects of thirst experiences, whereas activity in neocerebellar (posterior) regions may be related to sensory and cognitive aspects. Moreover, the cerebellum is apparently not involved in the computation of thirst per se but rather is activated during changes in thirst/satiation state when the brain is "vigilant" and is monitoring its sensory systems. Some neocerebellar activity may also reflect an intentionality for gratification by drinking inherent in the consciousness of thirst.

Adult↗
PubMed2000

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Journal Article↗
PubMed1999

Neuroimaging of genesis and satiation of thirst and an interoceptor-driven theory of origins of primary consciousness.

There are defined hypothalamic functions in the genesis of thirst, but little is known of the cortical processes subserving consciousness of thirst notwithstanding the medical disorders that occur in psychiatric illness, addiction, and the attested decline of thirst with aging. In 10 adult males, positron emission tomography scans were made (i) during genesis of moderate thirst by infusion of i.v. hypertonic saline 0.51 M, (ii) after irrigation of the mouth with water to remove the sensation of dryness, and (iii) 3, 14, 45, and 60 minutes after drinking water to fully satiate thirst. The correlation of regional cerebral blood flow with thirst score showed the major activation to be in the posterior cingulate. Maximum thirst sensation evoked 13 highly significant activations and 9 deactivations in cingulate and parahippocampal gyri, insula, thalamus, amygdala, and mesencephalon. It is possible that cingulate sites (Brodmann's areas 32, 24, and 31) that persisted with wet mouth but disappeared immediately after drinking to satiation may have an important role in the consciousness of thirst. Consciousness of thirst, a primal vegetative emotion, and satiation of thirst appear to be subserved by phylogenetically ancient brain regions. This is salient to current discussion on evolutionary emergence of primary consciousness.

Adult↗
PubMed1999

Correlation of regional cerebral blood flow and change of plasma sodium concentration during genesis and satiation of thirst.

Positron emission tomography studies were conducted during genesis of moderate thirst by rapid i.v. infusion of hypertonic saline (0.51 M) and after satiation of thirst by drinking water. The correlation of regional cerebral blood flow with the change in the plasma Na concentration showed a significant group of cerebral activations in the anterior cingulate region and also a site in the middle temporal gyrus and in the periaqueductal gray. Strongest deactivations occurred in the parahippocampal and frontal gyri. The data are consistent with an important role of the anterior cingulate in the genesis of thirst.

Adult↗
PubMed1997

Characterization of dynamic 3-D PET imaging for functional brain mapping.

Methods for optimizing the acquisition, reconstruction and analysis of positron emission tomography (PET) images for functional brain mapping have been investigated. The scatter fraction and noise-equivalent count rate characteristics were measured for the ECAT 951/31R PET scanner operating in septa-extended two-dimensional (2-D) and septa-retracted three-dimensional (3-D) modes. The 3-D mode is shown to provide higher signal-to-noise images than the 2-D mode at specific activities less than 30 kBq/ml. To enable increased temporal resolution in dynamic 3-D PET activation studies, a parallel version of the 3-D reconstruction algorithm was developed. Implementation of the reprojection algorithm on an 88 processor 1860 supercomputer resulted in a more than tenfold increase in reconstruction speed compared to a single 1860 processor system. An investigation of the optimal duration for imaging brain activations was undertaken in 12 normal subjects using repeated H2(15)O slow infusions and a visually presented lexical decision task. The significance of change in regional cerebral blood flow (CBF) was determined using statistical parametric maps for images acquired during stimulation, immediately after stimulation, and commencing 1 min after cessation of the stimulus. Regions of CBF change were detected in all three images. Dynamic 3-D, or four-dimensional (4-D), PET activation scanning is shown to be practical and likely to further improve the sensitivity of PET for detection of subtle regional CBF changes in functional brain mapping research.

Adult↗
PubMed1991

Dose distribution following selective internal radiation therapy.

Selective Internal Radiation Therapy is the intrahepatic arterial injection of microspheres labelled with 90Y. The microspheres lodge in the precapillary circulation of tumor resulting in internal radiation therapy. The activity of the 90Y injected is managed by successive administrations of labelled microspheres and after each injection probing the liver with a calibrated beta probe to assess the dose to the superficial layers of normal tissue. Predicted doses of 75 Gy have been delivered without subsequent evidence of radiation damage to normal cells. This contrasts with the complications resulting from doses in excess of 30 Gy delivered from external beam radiotherapy. Detailed analysis of microsphere distribution in a cubic centimeter of normal liver and the calculation of dose to a 3-dimensional fine grid has shown that the radiation distribution created by the finite size and distribution of the microspheres results in an highly heterogeneous dose pattern. It has been shown that a third of normal liver will receive less than 33.7% of the dose predicted by assuming an homogeneous distribution of 90Y.

Humans↗
PubMed1990

Increased H-2Dd expression following infection by a molecularly cloned ecotropic MuLV.

The biological consequences of radiation leukemia virus (RadLV) infection include the stimulation of H-2Dd antigen expression in resistant mouse strains and thymoma induction in susceptible strains. In an effort to understand the genetic basis of these phenomena, the integrated ecotropic RadLV genome has been examined in a number of primary RadLV-induced tumors, as well as thymomas adapted to in vitro passage; considerable heterogeneity was observed. Examination of these polymorphic viral sequences should help define the viral gene(s) involved in the biological effects of RadLV infection; toward this end, integrated RadLV genomes were molecularly cloned and examined. The genomes and their flanking sequence were characterized by restriction enzyme analysis. Three unique viral genomes were obtained which represent four integration sites. The three RadLV genomes are shown to carry polymorphisms of the original tumor. Following DNA transfection, one of the three genomes replicated in and reinfected both mouse thymocytes and fibroblasts, but not mink fibroblasts in vitro. Virus encoded by the other two DNA genomes could not be recovered following transfection into any of the three cell types. One of these two apparently defective retroviruses encodes a truncated p15E molecule, while the other has elongated long terminal repeats (LTRs). The non-defective ecotropic isolate was collected from in vitro tissue culture supernatants, concentrated, and used to infect mice. Thymocytes of infected, resistant mice were shown to express elevated levels of H-2Dd antigen as early as 12 days post infection, a hallmark of RadLV infection.

Animals↗
PubMed1988

Extension of the H-2 TLb molecular map. Isolation and characterization of T13, T14, and T15 from the C57BL/6 mouse.

A region of the TLb locus encompassing T11 to T13 contains retroviral sequences TLev1 and TLev2. As part of a study to determine whether the retroviral elements are involved in the expression of TL genes, the genomic organization of this region was reexamined in greater detail. A result of these investigations is the extension of the H-2 TLb molecular map. Two additional TL genes have been isolated from C57BL/6 mice, T14 and T15. The genomic organization of T9 through T15 is presented. The nucleotide sequence has been determined for exons 4, 5, and 6 of T13. As a result of a C to T conversion, a termination codon is introduced into exon 4, indicating that T13 either encodes a secreted protein or is a pseudogene. T13 was found to be more homologous to the H-2 genes outside the TL region. T14 has been physically disrupted by the integration of TLev1, and the H-2 sequences appear to have diverged greatly. The relationship of the TL regions of the b and c haplotypes has been investigated using numerous low copy probes. The genome of BALB/c (TLc) is shown to lack a counterpart of the T13-T15b region. Homologous regions exist in the two haplotypes; yet considerable polymorphism is observed. TLb mice do not express TLa on the cell surface of normal thymocytes while TLc mice do; TLa expression is activated in many TLb leukemias. The diversity seen in the T13-T15 region may provide insights into the phenotypic expression or regulatory mechanisms of TL expression in these two haplotypes.

Animals↗
PubMed1985

Covert cross reactants in a two-site immunoassay studied with monoclonal antibodies.

A one-step two-site immunoradiometric assay for the measurement of free beta subunit of human chorionic gonadotrophin (beta-hCG) was developed using monoclonal antibodies. The immobilized antibody was specific for free beta subunit and the radiolabeled antibody recognized both intact human chorionic gonadotrophin (hCG) and free beta subunit. Although the level of hCG "cross-reaction" was low when studied using conventional techniques, the apparent beta-hCG content of samples was found to be inversely proportional to the hCG level. From both experimental evidence and computer simulation studies this was found to be due to the binding of hCG to the limited amount of 125I-labeled antibody present. The term covert cross reactants has been introduced to describe substances which bind to only one of the antibodies in a two-site immunoassay. When establishing such an assay the effect of covert cross reactants on the response of an analyte should be investigated.

Antibodies, Monoclonal↗
PubMed1984

The evaluation of imprecision in collaborative immunoassay quality-assessment programmes.

The calculation of within-laboratory imprecision in quality-assessment (QA) programmes normally involves combining data from different analyte concentrations to calculate an average standard deviation (SD) or coefficient of variation. However, for immunoassay neither of these parameters is concentration independent. This paper describes a method of calculating within-laboratory imprecision in QA programmes by assuming a linear relationship between SD and analyte concentration. This method is used in programmes conducted by the Australian Joint Working Party for Quality Control in Immunoassay to calculate imprecision at the limits of the reference range. Results from these programmes show that this method better represents the differences in imprecision between analytes, methods and laboratories than the calculation of a single imprecision parameter. The method is trivial for a computer and its robustness has been validated by Monte Carlo simulation. It is suggested that major differences in laboratory performance between different QA programmes may be due to inappropriate calculation of single imprecision parameters.

Humans↗