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Biomedical subjects

J Gee

Publications and source records attributed to J Gee.

At least 19 recordsLinked to original sources

Dissociation of numbers and objects in corticobasal degeneration and semantic dementia.

BACKGROUND: Semantic memory is thought to consist of category-specific representations of knowledge that may be selectively compromised in patients with neurodegenerative diseases, but this has been difficult to demonstrate reliably across object categories. METHODS: The authors evaluated performance on several simple measures requiring number representations (including addition and magnitude judgments of single digits), and on a task that requires object representations (an object naming task) in patients with corticobasal degeneration (CBD; n = 13) and semantic dementia (SD; n = 15). They also examined regional cortical atrophy using voxel-based morphometric analyses of high resolution structural MRI in subgroups of five CBD patients and three SD patients. RESULTS: CBD patients were consistently more impaired on simple addition and magnitude judgment tasks requiring number representations compared to object representations. Impaired performance with numbers in CBD was associated with cortical atrophy in right parietal cortex. By comparison, SD patients demonstrated a greater impairment on a naming task requiring object representations relative to their performance on measures involving number representations. This was associated with left anterior temporal cortical atrophy. CONCLUSION: The cognitive and neuroanatomic dissociations between CBD and SD are consistent with the hypothesis that number and object representations constitute distinct domains in semantic memory, and these domains appear to be associated with distinct neural substrates.

Aged↗

Grammatical and resource components of sentence processing in Parkinson's disease: an fMRI study.

BACKGROUND: Sentence comprehension requires linguistic processing as well as cognitive resources such as working memory (WM) and information-processing speed (IPS). The authors hypothesize that sentence comprehension difficulty in patients with mild PD is due to degradation of the large-scale neural network that supports cognitive resources during sentence processing. OBJECTIVE: To understand the neural basis for sentence comprehension difficulty in PD. METHOD: Regional brain activity with blood oxygenation level-dependent fMRI was monitored while seven PD patients and nine healthy seniors answered a simple probe about written sentences that vary in their grammatical and cognitive resource properties. RESULTS: Healthy seniors recruited posterolateral temporal and ventral inferior frontal regions of the left hemisphere, brain regions associated with grammatical processing that were also activated by PD patients. Healthy seniors also recruited left dorsal inferior frontal, right posterolateral temporal, and striatal regions that are associated with cognitive resources during sentence processing. Direct contrasts showed that striatal, anteromedial prefrontal, and right temporal regions are recruited to a significantly lesser degree in PD, but these patients have increased activation of right inferior frontal and left posterolateral temporal-parietal areas during sentence comprehension. CONCLUSION: These findings associate impaired sentence comprehension in PD with interruption of a large-scale network important for cognitive resources during sentence processing. These results also imply compensatory up-regulation of cortical activity that allows patients with mild PD to maintain sentence comprehension accuracy.

Aged↗

An fMRI study of sex differences in regional activation to a verbal and a spatial task.

Sex differences in cognitive performance have been documented, women performing better on some phonological tasks and men on spatial tasks. An earlier fMRI study suggested sex differences in distributed brain activation during phonological processing, with bilateral activation seen in women while men showed primarily left-lateralized activation. This blood oxygen level-dependent fMRI study examined sex differences (14 men, 13 women) in activation for a spatial task (judgment of line orientation) compared to a verbal-reasoning task (analogies) that does not typically show sex differences. Task difficulty was manipulated. Hypothesized ROI-based analysis documented the expected left-lateralized changes for the verbal task in the inferior parietal and planum temporal regions in both men and women, but only men showed right-lateralized increase for the spatial task in these regions. Image-based analysis revealed a distributed network of cortical regions activated by the tasks, which consisted of the lateral frontal, medial frontal, mid-temporal, occipitoparietal, and occipital regions. The activation was more left lateralized for the verbal and more right for the spatial tasks, but men also showed some left activation for the spatial task, which was not seen in women. Increased task difficulty produced more distributed activation for the verbal and more circumscribed activation for the spatial task. The results suggest that failure to activate the appropriate hemisphere in regions directly involved in task performance may explain certain sex differences in performance. They also extend, for a spatial task, the principle that bilateral activation in a distributed cognitive system underlies sex differences in performance.

Brain↗

Androgen-metabolizing enzymes show region-specific changes across the breeding season in the brain of a wild songbird.

The Lapland longspur (Calcarius lapponicus) is an arctic-breeding songbird that shows rapid behavioral changes during a short breeding season. Changes in plasma testosterone (T) in the spring are correlated with singing but not territorial aggression in males. Also, T treatment increases song but not aggression in this species. In contrast, in temperate-zone breeders, song and aggression are highly correlated, and both increase after T treatment. We asked whether regional or temporal differences in androgen-metabolizing enzymes in the longspur brain explain hormone-behavior patterns in this species. We measured the activities of aromatase, 5alpha-reductase and 5beta-reductase in free-living longspur males. Aromatase and 5alpha-reductase convert T into the active steroids 17beta-estradiol (E(2)) and 5alpha-dihydrotestosterone (5alpha-DHT), respectively. 5beta-Reductase deactivates T via conversion to 5beta-DHT, an inactive steroid. We examined seven brain regions at three stages in the breeding season. Overall, aromatase activity was high in the hypothalamus, hippocampus, and ventromedial telencephalon (containing nucleus taeniae, the avian homologue to the amygdala). 5beta-Reductase activity was high throughout the telencephalon. Activities of all three enzymes changed over time in a region-specific manner. In particular, aromatase activity in the rostral hypothalamus was decreased late in the breeding season, which may explain why T treatment at this time does not increase aggression. Changes in 5beta-reductase do not explain the effects of plasma T on aggressive behavior.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Characterization of maternal influence on teratogenicity: an assessment of developmental toxicity studies for the herbicide cyanazine.

The contribution of maternal toxicity to the teratogenic effects of the herbicide cyanazine has been assessed to determine whether it may be a hazard to development. Eye defects such as anophthalmia and microphthalmia were observed in rat fetuses and pups. Maternal toxicity was determined from body weight data and clinical signs. Two approaches were used. First, the timing of maternal toxicity was correlated with the specific period of gestation during which the observed fetal defect was most likely to have occurred. Second, individual dams, as well as mean values for each group, were evaluated. The data at the individual level, i.e., in dams with affected litters, did not support conclusions based on the group means. Instead, it is suggested that the developmental effects were not a direct result of maternal toxicity of cyanazine. Data from a rabbit developmental toxicity study supported the findings from the Fischer 344 rat studies. The strategy employed may thus enable direct toxicity to the fetus to be distinguished from developmental toxicity arising as a secondary consequence of maternal toxicity.

Abnormalities, Drug-Induced↗

Laparoscopic repair of ureterosciatic hernia.

Ureterosciatic herniation is a rare benign event that can mimic diverticulosis or irritable bowel syndrome. This entity has been managed by a number of open surgical techniques. Laparoscopic repair of this entity enabled us to identify the defect, interpose mesh, and obliterate the hernia defect with minimal morbidity. This represents the first report of laparoscopic repair of a ureterosciatic hernia.

Female↗

Age-related differences in the effect of dichloroacetate on postischemic lactate and acid clearance measured in vivo using magnetic resonance spectroscopy and microdialysis.

Numerous studies using adult animal models suggest that dichloroacetate (DCA) may have neuroprotective properties by virtue of its ability to increase rates of metabolism and, therefore, clearance of brain lactic acidosis, which may accumulate during cerebral ischemia. We tested the hypothesis that postischemic DCA administration affects lactate and acid clearance to different extents in immature versus mature brain. 31P and 1H magnetic resonance spectroscopy were used to measure intracellular acid and lactate clearance rates in vivo in newborn and 1-month-old swine after a 14-min episode of transient near-complete global ischemia. Simultaneous monitoring of extracellular lactate efflux and clearance was measured in the same animals by in vivo microdialysis. Plasma glucose concentrations were elevated in order to study animals with severe cerebral lactic acidosis. Maximal levels of brain lactosis (16-20 micromol/g) and acidosis (PHintracellular 5.8-6.0) were reached during the first 10 min of recovery and were the same in age groups and in subgroups either acting as controls or treated with DCA (200 mg/kg) given from the last minute of ischemia to 5-7 min after ischemia. For newborns, DCA administration improved the postischemic clearance rate of cerebral acidosis and cerebral phosphocreatine, with similar trends for the clearance of lactosis and increased rates of recovery of nucleotide triphosphates, compared with controls. In contrast, DCA administration in 1-month-olds resulted in a modest trend for improvement of cerebral lactate clearance, but did not affect acid clearance or the recovery rate of phosphocreatine or nucleotide triphosphates. Extracellular brain lactate concentrations had similar relative increases and rates of decline for subgroups of either age treated with DCA versus controls. The results of this study indicate that postischemic DCA administration helps to resolve cerebral acidosis to a greater degree in immature than more mature brain, suggesting that DCA may have cerebroprotective properties for neonatal hypoxic-ischemic encephalopathy.

Acids↗

Nuances of aesthetic blepharoplasty.

The orbits and surrounding tissues form the emotional and expressive center of the human face. Eye contact forms a large part of human interaction and, unfortunately, it is often this region that first surrenders to the aging process. A successful blepharoplasty depends on the careful evaluation of a patient's eyes, correct assessment of the cosmetic problems, and the surgical dexterity to repair such defects adequately. Consistent success may be achieved only with mastery of aesthetic consideration of the eyes, which aid in the diagnosis of the deformity of asymmetry. From that, the appropriate surgical intervention may ensue. This discussion will review the anatomy related to different orbital expressions, delineate the effects of aging, and briefly touch on techniques in our surgical armamentarium to correct and improve eyes through blepharoplasty.

Adult↗

Investigation of oestrogen receptors, sex steroids and soluble adhesion molecules in the progression of malignant melanoma.

The question of whether melanoma tumours have classical oestrogen receptors (ERs) is unresolved, but epidemiological data clearly show a survival benefit for female patients with metastatic melanoma. The aims of this study were to examine to what extent the presence of ER in melanoma tumours might relate to disease progression and whether disease progression relates to patients' sex steroid status. Additionally, levels of two soluble adhesion molecules [circulating intercellular adhesion molecule-1 (sICAM-1) and circulating vascular cell adhesion molecule-1 (sVCAM-1)] were examined as independent, possibly prognostic indicators of disease progression. ER immunocytochemical assay identified only two lesions (out of 69 investigated) which had any evidence of the receptors, and staining in these lesions was very modest. No significant changes in oestrone or androstenedione levels were noted for male or female patients with disease progression. As expected, oestradiol levels reflected the menopausal status of the female patients but, for all post-menopausal female patients and male patients, there was no significant relationship to tumour stage. However, a significant decrease in sex hormone-binding globulin occurred with disease progression in male but not female patients, and sex differences in the levels of soluble adhesion molecules were also seen in advanced metastatic disease.

Adolescent↗

Calculation of intracellular cerebral [Mg2+] during hypoxic ischemia by in vivo 31P NMR.

Several algorithms for the calculation of ionized intracellular magnesium concentration from the chemical shifts of MgATP were compared, using in vivo 31P NMR data obtained from swine brain during and following hypoxic ischemia plus i.v. MgSO4 infusion. This analysis reveals that both the absolute ionized intracellular magnesium and relative changes in magnesium may vary widely between algorithms used. The calculated intracellular pH, used in algorithms to determine ionized magnesium concentration was found to be a critical parameter that governs the extent of these differences.

Adenosine Triphosphate↗

Alcohol and preoperative management.

The French paradox is a recently coined term used to describe the lower incidence of heart disease in the French as compared with Americans in the face of increased cholesterol intake, higher serum cholesterol levels, and elevated blood pressures. The principal lifestyle factor explaining this paradox is alcohol intake. Research has shown that alcohol in general and wine in particular have myriad effects on the cardiovascular system--raising high-density lipoprotein levels, increasing antioxidant capabilities, and prolonging platelet aggregation. The most impressive benefits of alcohol appear to be platelet-related. Research has demonstrated an undeniable effect of alcohol on platelet function and bleeding characteristics. This information has been used recently to modify risk factors for heart disease; however, these data have a role in the preoperative management of surgical patients. In order to decrease the incidence and severity of intraoperative and postoperative bleeding, patients should be advised to abstain from alcohol and particularly red wine before surgery. In addition, alcohol has been found to have a synergistic effect with aspirin on bleeding times. These two substances, both individually and in combination, should be avoided preoperatively.

Animals↗

Aquatic surface respiration, buoyancy control and the evolution of air-breathing in gobies (Gobiidae: Pisces)

The role of a buccal gas bubble, held while performing aquatic surface respiration (ASR; ventilating the gills with surface water during hypoxia), was examined in benthic, intertidal Australian gobies (Favonigobius tamarensis, F. exquisitus, Pseudogobius olorum, Chlamydogobius sp., Mugilogobius paludis, Cryptocentroides cristatus and Arenigobius bifrenatus). Analyses of the forces of lift and weight of the head and body during ASR indicate a hydrostatic role for the bubble. During ASR, lift from the bubble was sufficient to provide neutral or positive buoyancy to the head, anchoring the mouth at the water surface. A buoyancy role was confirmed by experiments demonstrating the ability of some species to alter bubble volume, to compensate either for different body positions or for water densities (salinities). Use of the bubble for aerial respiration by Cryptocentroides, Mugilogobius, Chlamydogobius and Arenigobius was confirmed in hypoxia by the presence of blood-filled capillaries in the buccal subepithelium (mean air­blood barrier less than 30 µm) in areas of the buccal cavity that contacted the bubble. Blood-filled capillaries were rare or absent in normoxia in all species except Mugilogobius. Cutaneous respiration was inferred from the presence of blood-filled capillaries in the dermis and epidermis of emersed portions of the head in Mugilogobius, Chlamydogobius and Arenigobius. The buccal bubble has respiratory and hydrostatic roles and there is support for the hypothesis that ASR and the buoyancy regulation (air-gulping) required to perform it effectively are prerequisite steps in the evolution of air-breathing in these gobies.

Journal Article↗

Triplex formation by the human Ha-ras promoter inhibits Sp1 binding and in vitro transcription.

The central role of the ras oncogenes in the pathogenesis of a wide variety of human malignancies is well established. Toward developing specific transcriptional inhibitors of the human Ha-ras oncogene, we have designed oligonucleotides to target a region of the Ha-ras promoter (-8 to -28) which contains two of the three Sp1 binding sites essential for transcriptional activity. Gel mobility analysis and DNase I footprinting demonstrate that an oligonucleotide (HR21ap) forms a sequence-specific triple helix with its target site in an antiparallel orientation with respect to the purine-rich duplex strand through predominantly G*G:C triplets. Within the Ha-ras promoter, HR21ap binds exclusively to the proximal target Sp1 sites over a similar nontarget distal sequence which, like the target, contains a consensus Sp1 site. Protein binding assays demonstrate that triplex formation by HR21ap inhibits Sp1 binding to the Ha-ras promoter. Moreover, oligonucleotide-directed triplex formation arrests Ha-ras promoter-dependent transcription in vitro. The results presented here suggest that triplex formation by the Ha-ras promoter targeted oligonucleotide may provide a means to specifically inhibit transcription of this oncogene in vivo.

Base Sequence↗

Dual immunocytochemical analysis of oestrogen and epidermal growth factor receptors in human breast cancer.

Recent studies have demonstrated a consistent inverse relationship between oestrogen receptor (ER) and epidermal growth factor receptor (EGFR) levels in female human breast cancer. Serial cross-section studies have suggested that separate populations of ER+/EGFR- and ER-/EGFR+ cancer cells exist in tumours deemed by immunocytochemical assay (ICA) to be positive for both. We have developed a dual ICA that is able to stain for both ER and EGFR on a single 5 microns frozen section sample of breast tissue. Twenty-two samples of female human breast cancer tissue that exhibited positivity for ER and EGFR by ER-ICA using the H222 monoclonal antibody and EGFR-ICA using the EGFR1 monoclonal antibody underwent the dual ICA. There was a significant correlation in receptor positivity between the single and dual assays for both ER (rs = 0.801, P < 0.001) and EGFR (rs = 0.831, P < 0.001). Individual cancer cells exhibited one of three staining patterns: nuclear staining only (ER+/EGFR-), membrane-associated and cytoplasmic staining only (ER-/EGFR+) or no staining (ER-/EGFR-). No cancer cells exhibited both nuclear and membrane/cytoplasmic staining. This is the first description of a simultaneous dual immunocytochemical assay system for ER and EGFR in clinical breast cancer specimens. The results suggest that ER and EGFR expression are mutually exclusive within an individual breast cancer cell in vivo with separate populations of ER+/EGFR- cells, ER-/EGFR+ cells and ER-/EGFR- cells coexisting.

Adult↗

Upregulation of renin-angiotensin system and downregulation of kallikrein in obstructive nephropathy.

The purpose of this study was to delineate the effects of prolonged (1 and 5 wk) unilateral ureteral obstruction (UUO) on the intrarenal renin-angiotensin and kallikrein-kinin systems in the rat. Systolic blood pressure (SBP) and plasma angiotensin (ANG) II levels were significantly higher at 1 and 5 wk of obstruction than in sham-operated groups. Also, plasma renin activity and ANG I levels were elevated at 1 wk (P < 0.05), and plasma angiotensin-converting enzyme (ACE)-kininase II activity was elevated at 5 wk (P < 0.05). Blockade of ANG II receptors with losartan (Dup 753) prevented the rise in SBP after UUO and normalized SBP in chronically hypertensive UUO rats. Renin mRNA levels and ANG II content were elevated in the obstructed kidneys at 1 and 5 wk compared with sham-operated kidneys (P < 0.05). ACE-kininase II activity was elevated in both the obstructed and contralateral kidneys at 5 wk compared with sham-operated kidneys (P < 0.05). In marked contrast to renin, total immunoreactive kallikrein contents and tissue kallikrein mRNA levels in the obstructed kidneys were reduced to 25% of sham-operated kidneys both at 1 and 5 wk (P < 0.001). The results indicate that urinary obstruction activates renin and suppresses kallikrein gene expression. Activation of ACE-kininase II by UUO also serves to enhance intrarenal ANG II generation and kinin degradation. The results implicate ANG II overproduction and kinin deficiency in the pathogenesis of UUO-induced hypertension and intrarenal vasoconstriction.

Angiotensin II↗