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Biomedical subjects

J Goodman

Publications and source records attributed to J Goodman.

At least 37 records · Page 2Linked to original sources

Eye tracking disorder in schizophrenia is characterized by specific ocular motor defects and is associated with the deficit syndrome.

The objective was to determine the relationships between eye tracking disorder (ETD) in schizophrenia, specific ocular motor measures, and the deficit syndrome. Twenty-five normal comparison subjects and 53 schizophrenic patients had eye movements tested with infrared oculography using a sinusoidal target. Patients were assessed with the Schedule for the Deficit Syndrome. For the patients, the distribution of position root mean square error (a global measure of pursuit) was best fit by a mixture of two normal distributions. This information was used to divide the patients into two subgroups, those with and those without ETD. ETD was almost completely accounted for by several specific ocular motor measures and was significantly associated with the deficit syndrome. The finding that ETD was almost completely accounted for by specific measures bridges a gap of interpretation in this field. ETD and the deficit syndrome of schizophrenia may share a common pathophysiology of cerebral cortical-subcortical circuits.

Adult↗

Overregularization in English plural and past tense inflectional morphology: a response to Marcus (1995).

In a recent note, Marcus (1995) suggests that the rate of overregularization of English irregular plural nouns is not substantively different from that of English irregular past tense verbs. This finding is claimed to be in conflict with the predictions of connectionist models (Plunkett & Marchman, 1991, 1993) which are said to depend solely on the dominance of regular over irregular forms in determining overregulation errors. However, these conclusions may be premature given that Marcus averaged overregulation rates across irregular nominal forms that varied in token frequency and across samples representing a broad range of children's ages. A connectionist view would predict an interplay between type frequency and other item level factors, e.g. token frequency, as well as differences in the developmental trajectories of the acquisition of nouns and verbs. In this response, we briefly review longitudinal parental report data (N = 26) which indicate that children are significantly more likely to produce noun overregularizations than verb overregularizations across a prescribed age period (1:5 to 2:6). At the same time, these data also show that children are familiar with proportionately more irregular nouns than irregular verbs. These findings are consistent with the predictions of Plunkett & Marchman (1991, 1993) in that the larger regular class affects the frequency of noun errors but also that familiarity with individual irregular nouns tends to reduce the likelihood of overregularizations. In contrast to the conclusion of Marcus (1995), the connectionist approach to English inflectional morphology provides a plausible explanation of the phenomenon of overregularization in both the English plural and past tense systems.

Child Language↗

Exposure to low oxygen tension and increased osmolarity enhance the ability of Mycobacterium avium to enter intestinal epithelial (HT-29) cells.

Current evidence indicates that Mycobacterium avium infection in patients with AIDS is acquired mostly through the gastrointestinal (GI) tract and that M. avium binds to and invades GI mucosal cells in vitro. Since M. avium is exposed to specific environmental conditions in the GI tract such as changes in pH, low oxygen (O2) tension, increased osmolarity, and low concentration of iron, we investigated the effects of these conditions on the bacterium's ability to enter HT-29 intestinal cells. M. avium 101 (serovar 1) was cultured in 7H9 broth and then exposed to pH 4.5 to 8.0, low O2 tension, 0.1 to 0.3 M dextrose, and absence of iron for 2 h. After washing, bacteria (10(7)/ml) were used in the invasion assay. Confluent HT-29 cells were exposed to 10(6) bacteria for 1 h and then treated with amikacin (200 microg/ml) for 2 h to selectively kill extracellular but not intracellular M. avium. The supernatant was then removed, the monolayer was lysed, and the lysate was plated onto 7H10 agar plates. While exposure to acidic and basic pHs, as well as iron-free medium, had no significant effect on M. avium invasion of intestinal epithelial cells, low O2 tension and increased osmolarity enhanced invasion 11- and 9-fold, respectively, compared with the control. Exposure of M. avium to the combination of low O2 concentration and hyperosmolarity resulted in an approximate 10- to 15-fold increase in penetration of HT-29 cells. Hyperosmolarity and low O2 tension induced the invasive M. avium phenotype and can be useful for the identification of genes associated with M. avium invasion of intestinal mucosa.

Amikacin↗

Creatine ingestion increases anaerobic capacity and maximum accumulated oxygen deficit.

The purpose of this study was to test the hypothesis that ingestion of creatine monohydrate increases anaerobic exercise capacity, as reflected by the maximal accumulated oxygen deficit (MAOD). Subjects were assigned, double-blind, to placebo (PL, n = 12) or creatine (CR, n = 14) groups and ingested 5-g doses 4 times daily of artificial sweetener or artificially sweetened creatine monohydrate, respectively, for 5 days. On a separate day subjects exercised to exhaustion at 125% VO2max. After two familiarization trials, MAOD was again determined before treatment, after 5 days of PL or CR treatment, and 7 days later. MAOD increased after CR treatment from 4.04 +/- 0.31 to 4.41 +/- 0.34 L (p < .001) and remained elevated for another 7 days (4.31 +/- 0.33, p < .001). Time to exhaustion also increased in CR from 130 +/- 7 to 141 +/- 7 s (p < .01) and remained increased for another 7 days (139 +/- 8 s, p < .01). These data demonstrate that ingesting creatine monohydrate for 5 days increases the MAOD, and is likely to have an ergogenic effect on supramaximal exercise performance that persists for at least a week after treatment.

Administration, Oral↗

Brain and erythrocyte anion transporter protein, band 3, as a marker for Alzheimer's disease: structural changes detected by electron microscopy, phosphorylation, and antibodies.

Band 3, a ubiquitous membrane transport, regulatory, and structural protein, is represented in brain by at least 4 isoforms. Bands 3 in brain performs the same functions as it does in erythrocytes (RBC). It is susceptible to oxidative damage, which, ultimately, terminates its life and that of the cell. We examined the changes band 3 undergoes in Alzheimer's disease (AD) because our previous studies suggest that band 3 is a pivotal protein in neurological disease. Because we hypothesize that AD is a total body disease, we examined peripheral blood cells as well as brain tissue to determine whether the same changes occur in both. Our results indicate that posttranslational changes occur in RBC band 3 that parallel changes in brain band 3. These include decreased 32P-phosphate labeling in vitro of band 3 polypeptides in brain and RBC, increased degradation of band 3, alteration in band 3 recognized by polyclonal and monoclonal antibodies, and decreased anion and glucose transport by blood cells. Serum autoantibodies to band 3 peptides 588-602 and 822-839 were increased in AD patients compared to controls. These band 3 residues lie in anion transport/binding regions. This is consistent with alteration of this region in AD since it is recognized as antigenically different by the patients' immune system. Our data support an immunological component to AD. The finding that changes in RBC in AD reflect those in brain and can be recognized by antibodies should facilitate development of blood tests for diagnosis and monitoring, and early therapy. It is anticipated that identification of molecular sites of posttranslational modification of band 3 will enable us to design specific preventive and treatment strategies, and target drugs to crucial molecular sites.

Aging↗

Mesenchymal-epithelial interactions in the bladder.

During bladder development, undifferentiated mesenchymal and epithelial cells undergo an orderly sequence of differentiation defined by the expression of smooth-muscle (alpha-actin, myosin, vinculin, desmin, vimentin, and laminin) and epithelial (cytokeratins 5, 7, 8, 14, 18 and 19) protein markers. This process requires mesenchymal-epithelial interactions with bladder epithelium (urothelium) necessary for the differentiation of bladder smooth muscle. Peptide growth factors such as keratinocyte growth factor (KGF) and transforming growth factors (TGF) alpha and beta are likely candidates as mediators of these mesenchymal-epithelial interactions. Transcripts for KGF, TGF alpha, and TGF beta are regulated during bladder development and during smooth-muscle hypertrophy secondary to bladder-outlet obstruction. Finally, two experimental bladder models--(1) partial outlet obstruction and (2) regeneration of bladder smooth muscle into an acellular tissue matrix--are described in the context of mesenchymal-epithelial interactions in the bladder.

Animals↗

Tracheal gas insufflation is a useful adjunct in permissive hypercapnic management of acute respiratory distress syndrome.

BACKGROUND: Despite numerous advances in critical care, the mortality of postinjury acute respiratory distress syndrome (ARDS) remains high. Recently, permissive hypercapnia (PHC) has been shown to be a viable alternative to traditional ventilator management in patients with ARDS. However, lowering tidal volume, as employed in PHC, below 5 cc/kg impinges upon anatomic dead space and precipitates a significant rise in PaCO2 The purpose of this study was to determine if continuous tracheal gas insufflation (cTGI) is a useful adjunct to PHC by lowering PaCO2, thus allowing adequate reduction in minute ventilation to achieve alveolar protection. METHODS: Over a 5-year period, 68 trauma patients with ARDS were placed on permissive hypercapnia. Nine of these patients additionally received cTGI at 7 L/min. Arterial blood gas determinations and ventilatory parameters were examined immediately prior to the implementation of cTGI and after 6h. RESULTS: The cTGI produced significant improvement in pH (7.25 +/- 0.03 to 7.33 +/- 0.03), PaCO2 (72 +/- 5 to 59 +/- 5 torr), tidal volume (7.9 +/- 0.6 to 7.2 +/- 0.6 cc/kg), and minute ventilation (13 +/- 1 to 11 +/- 1 L/min; P < 0.05). CONCLUSIONS: Continuous TGI is a useful adjunct to permissive hypercapnia, allowing maintenance of an acceptable pH and PaCO2 while allowing further reduction in tidal volume and minute ventilation.

Adolescent↗

Esophageal and duodenal atresia in a fetus with Down's syndrome: prenatal sonographic features.

Ultrasound examination of a 22-week fetus demonstrated a grossly distended stomach and proximal duodenum, with a large cystic area in the chest. There was associated polyhydramnios. A presumptive diagnosis of duodenal atresia with a congenital diaphragmatic hernia was made. Analysis of a fetal blood sample showed that the fetus had Down's syndrome. Histological examination after termination of the pregnancy revealed the unusual combination of duodenal and esophageal atresia, with an intact diaphragm.

Adult↗

Ultrastructural dynamics of mitochondrial morphology in varying functional forms of human adrenal cortical adenoma.

Adrenal cortical mitochondria display an extensive capacity to adapt morphologically to the functional state of the adrenal cortical cell. In the present study, we have used transmission electron microscopy to analyze cortical tissues from 3 normal human adrenal glands (zona fasciculata and zona glomerulosa), and from 8 steroid-secreting adrenal cortical adenomas (3 cortisol-producing, 4 aldosterone-producing, and 1 progesterone-producing tumor), correlating both clinical and biochemical features with cellular ultrastructure. The morphology of mitochondria was related to the enzyme activity and steroid-biosynthetic capacity of each tumor. Cells from aldosterone-producing adenomas demonstrated a large number of elongated tubular mitochondria with characteristic bridging of inner membranes, producing a lamellar-type pattern. Cells from cortisol-producing adenomas showed large round mitochondria with vesicular or tubulovesicular inner membranes surrounded by a characteristic dilated smooth endoplasmic reticulum. A highly unusual progesterone-producing adenoma, in which a deficiency of 21 alpha-hydroxylase activity was demonstrated, showed a peculiar type of enlarged lamellar mitochondria with bright inner matrix and a reduced number of inner membranes. Therefore, the ultrastructural characteristics of adrenal cortical mitochondria appear to be potential markers for the differentiation of steroid-producing adenomas. These studies point to the possibility of a broader use of electron microscopy in the study of adrenal tumors.

Adenoma↗

Cross-validation of the Delirium Rating Scale in older patients.

OBJECTIVE: To cross-validate the Delirium Rating Scale (DRS). DESIGN: Cross-sectional. SETTING: Geriatric medicine and geriatric psychiatry assessment units and consultation services. PARTICIPANTS: A total of 104 older patients on the above services. MEASUREMENTS: Mini-Mental State Examination (MMSE) score, Barthel Index score, DRS score, Blessed Dementia Scale score, clinical diagnoses using DSM-III-R criteria. MAIN RESULTS: The mean DRS score was highest in the delirium group. Cronbach's alpha was .90, and inter-rater reliability of total scores was .91 (intra-class correlation). Receiver Operating Characteristic curve analysis showed that the area under the curve for the DRS was significantly higher than the MMSE as a test for delirium. At its published cutpoint of 10, the sensitivity of the DRS is .82 and the specificity is 94. The value at which the sensitivity of the DRS is .90 is 8, at which specificity is .82. CONCLUSIONS: The DRS appears to a feasible instrument. In a sample with a high proportion of delirious patients, it has acceptable measurement properties when used by expert observers.

Aged↗

Mycobacterium tuberculosis invades and replicates within type II alveolar cells.

Although Mycobacterium tuberculosis is assumed to infect primarily alveolar macrophages after being aspirated into the lung in aerosol form, it is plausible to hypothesize that M. tuberculosis can come in contact with alveolar epithelial cells upon arrival into the alveolar space. Therefore, as a first step toward investigation of the interaction between M. tuberculosis and alveolar epithelial cells, we examined the ability of M. tuberculosis to bind to and invade alveolar epithelial cells in vitro. The H37Rv and H37Ra strains of M. tuberculosis were cultured to mid-log phase and used in both adherence and invasion assays. The A549 human type II alveolar cell line was cultured to confluence in RPMI 1640 supplemented with 5% fetal bovine serum, L-glutamine, and nonessential amino acids. H37Rv was more efficient in entering A549 cells than H37Ra, Mycobacterium avium, and Escherichia coli Hb101, and nonpiliated strain (4.7% +/- 1.0% of the initial inoculum in 2 h compared with 3.1% +/- 0.8%, 2.1% +/- 0.9%, and 0.03% +/- 0.0%, respectively). The invasion was more efficient at 37 degrees C than 30 degrees C (4.7% +/- 1.0% compared with 2.3% +/- 0.8%). H37Rv and H37Ra were both capable of multiplying intracellularly at a similar ration over 4 days. Binding was inhibited up to 55.7% by anti-CD51 antibody (antivitronectin receptor), up to 55% with anti-CD29 antibody (beta(1) integrin), and 79% with both antibodies used together. Update of M. tuberculosis H37Rv was microtubule and microfilament dependent. It was inhibited by 6l.4% in the presence of 10 micron colchicine and by 72.3% in the presence of 3 micron cytochalasin D, suggesting two separate pathways for uptake. Our results show that M. tuberculosis is capable of invading type II alveolar epithelial cells and raise the possibility that invasion of alveolar epithelial cells is associated with the pathogenesis of lung infection.

Animals↗

Endurance-trained and untrained skeletal muscle bioenergetics observed with magnetic resonance spectroscopy.

Resting and submaximal isometric exercise 31P magnetic resonance spectroscopy (MRS) was carried out on 7 endurance-trained males (26.0 +/- 3 yrs) and 7 sedentary males (27.0 +/- 4 yrs). Spectral analysis provided peak areas of phosphocreatine (PCr), inorganic phosphate (Pi), adenosine triphosphate (ATP), and the chemical shift of Pi relative to PCr. The ratio of PCr/Pi was moderately lower during rest (preexercise p = .13, postexercise p = .18), and significantly higher during exercise (p < .05) in the trained subjects. Intracellular pH patterns were the same for both groups; a transient alkalosis was observed at the onset of exercise with a return to resting levels after 2 min. Differences suggest improved ATP resynthesis rate in the trained subjects during exercise. Intracellular pH changes can be attributed to the utilization of hydrogen ions that accompany PCr hydrolysis during work. The findings are congruent with previous reports indicating a superior oxidative capacity in trained skeletal muscle.

Adenosine Triphosphate↗

The role of calcitonin gene-related peptide and nitric oxide in gastric mucosal hyperemia and protection.

It has been suggested that capsaicin-induced hyperemia and mucosal protection occurs via calcitonin-gene-related peptide (CGRP) release from gastric afferent sensory neurons and nitric oxide (NO)-mediated vasodilation. The purpose of this study was to determine whether capsaicin and/or bile acid induced hyperemia is mediated by CGRP and/or NO. Male Sprague-Dawley rats (280-350 g) were anesthetized, and the glandular stomach (blood supply intact) was chambered between two plastic rings. Animals were divided into six groups. Normal saline (groups 1 and 4), the NO inhibitor N-nitro-L-arginine methyl ester (L-NAME; 3.75 mg/ml, groups 2 and 5), or the CGRP antagonist hCGRP8-37 (0.047 mg/ml, groups 3 and 6) was continuously infused intraarterially (ia) close to the stomach at a rate of 0.034 ml/min for 1 hr via a catheter inserted retrogradely into the splenic artery. Fifteen minutes after the onset of this infusion, the gastric mucosa was topically exposed to neutral saline solution for 15 min, followed by 160 microM capsaicin for 15 min. The mucosa was then injured by a 15-min exposure to either 5 mM acidified taurocholate (ATC, pH 1.2) in groups 1-3 or 10 mM ATC in groups 4-6. Gastric mucosal blood flow (ml/min/100 g) was continuously measured (laser doppler), and injury was assessed by measuring net transmucosal H+ flux, luminal accumulation of DNA, and histologic grading (0 = no injury to 3 = severe) by an independent observer. Intraarterial infusion of L-NAME significantly blocked the hyperemic response of topical capsaicin while having minimal effect on bile acid-induced hyperemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The association between small size for gestational age and perinatal and neonatal death in a UK Regional Health Authority.

Confidential enquiry into stillbirth and death in infancy is a health service requirement in England, Wales and Northern Ireland. A confidential review of perinatal death has been conducted in South-East Thames Region since 1988. Data collected for this review are analysed here. Among the 1662 singleton deaths in the enquiry from 1988 to 1991, 530 (32%) babies were small for gestational age (SGA < 10th centile): 338 of these (64%) were < 3rd centile and the remainder were between 3rd-10th centile. Small size for gestational age was significantly associated with a previous SGA baby (P = 0.02), proteinuric hypertension (P = 0.001) and increased placental-birthweight ratio (P = 0.008). Only 135 (25%) SGA fetuses were identified antenatally and multiple logistic regression showed that antenatal detection was independently related to proteinuric hypertension [odds ratio (OR) = 2.47, 95% confidence interval (CI) 1.47-4.17, P = 0.001) and to being < 3rd centile rather than 3rd-10th centile (OR = 3.16, 95% CI 1.96-5.10, P = 0.001). Although confidential enquiries have been criticised for a lack of objectivity the study indicates how data from such an enquiry can increase knowledge of events influencing peri- and neonatal outcome allowing strategies to be devised to effect change.

Data Collection↗