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J Harris

Publications and source records attributed to J Harris.

At least 91 records · Page 5Linked to original sources
PubMed2000

Modulation of the fish immune system by hormones.

Immune-neuroendocrine interactions in fish, as in mammals, have become a focus of considerable interest, with the modulation of immune responses by hormones receiving particular attention. Cortisol, growth hormone (GH), prolactin (PRL), reproductive hormones, melanin-concentrating hormone (MCH) and proopiomelanocortin (POMC)-derived peptides have all been shown to influence immune functions in a number of fish species. This review summarises the known effects of these hormones on the fish immune system, as well as the often complex interactions between different hormones. The possible implications for fish health, with respect to aquaculture and the changes in immunocompetence that take place during different stages in the fish life cycle are also discussed.

Animals↗
PubMed2000

A FE65 polymorphism associated with risk of developing sporadic late-onset alzheimer's disease but not with Abeta loading in brains.

The FE65 protein was previously described interacting with amyloid protein precursor (APP) and mediating its internalization. Hu et al. (Hum. Genet., 103 (1998) 295) recently reported that a deletion polymorphism in intron 13 of the FE65 gene may be protective for sporadic Alzheimer's disease (AD) forms and suggested that this deletion may modify splicing between exon 13 and 14 (the two exons encoding the interaction domain of FE65 with APP). We tested the impact of this polymorphism in 646 controls and 639 sporadic AD cases. We were only able to detect a protective effect of the deletion in the population over 75 years (odds ratio = 0.53, 95% confidence interval (0.35-0.82), P= 0.002). Furthermore, no association of this polymorphism with Abeta40, Abeta42(43) and total Abeta loads were detected in 74 AD brains, although, we could expect that this deletion was associated with modifications of the APP metabolism. In conclusion, the FE65 gene may be a minor genetic determinant only for sporadic late-onset AD forms, although, we cannot conclude that this impact is mediated by a modulation of the APP process and/or Abeta peptide deposition.

Age of Onset↗
PubMed2000

A major locus for myoclonus-dystonia maps to chromosome 7q in eight families.

Myoclonus-dystonia (M-D) is an autosomal dominant disorder characterized by myoclonic and dystonic muscle contractions that are often responsive to alcohol. The dopamine D2 receptor gene (DRD2) on chromosome 11q has been implicated in one family with this syndrome, and linkage to a 28-cM region on 7q has been reported in another. We performed genetic studies, using eight additional families with M-D, to assess these two loci. No evidence for linkage was found for 11q markers. However, all eight of these families showed linkage to chromosome 7 markers, with a combined multipoint LOD score of 11.71. Recombination events in the families define the disease gene within a 14-cM interval flanked by D7S2212 and D7S821. These data provide evidence for a major locus for M-D on chromosome 7q21.

Chromosome Mapping↗
PubMed2000

Supernatants from leucocytes treated with melanin-concentrating hormone (MCH) and alpha-melanocyte stimulating hormone (alpha-MSH) have a stimulatory effect on rainbow trout (Oncorhynchus mykiss) phagocytes in vitro.

Melanin-concentrating hormone (MCH) and alpha-melanocyte stimulating hormone (alpha-MSH) are widespread vertebrate neuropeptides. In teleost fish the peptides are involved in the hormonal control of skin pigmentation, but they have also been shown to modulate corticosteroid secretion in both fish and mammals. alpha-MSH has additional potent anti-inflammatory actions in mammals and both peptides stimulate leucocyte phagocytosis in rainbow trout in vitro. The effects of these peptides on phagocytosis and the release of immunomodulatory factors by rainbow trout head kidney leucocytes were investigated in vitro. Neither MCH nor alpha-MSH had any effect on the adherence of phagocytes to glass slides or the activity of isolated phagocytes. When added to mixed leucocyte suspensions, however, MCH (50 and 100nM) and alpha-MSH (1 and 10nM) significantly increased the percentage of cells undergoing phagocytosis and MCH (50nM), but not alpha-MSH, stimulated the phagocytic index. In subsequent experiments, isolated phagocytes were exposed to supernatants derived from mixed leucocyte suspensions exposed to MCH (50 and 100nM) and alpha-MSH (1 and 10nM). Supernatants from leucocytes exposed to all doses of the peptides significantly increased the percentage phagocytosis and those from cells stimulated with MCH (100nM) and alpha-MSH (1 and 10nM) increased the phagocytic index of the phagocytes. The results suggest that cells other than phagocytes are required for MCH and alpha-MSH to exert their stimulatory effects on trout phagocytic cells through the release of one or more macrophage-activating factors.

Animals↗
PubMed2000

Spinal anandamide inhibits nociceptive transmission via cannabinoid receptor activation in vivo.

The endocannabinoid anandamide has affinity for cannabinoid and vanilloid receptors, which have opposing effects on nociceptive transmission. Effects of spinal administration of anandamide on innocuous and noxious evoked spinal neuronal responses in non-inflamed and carrageenin-inflamed rats were studied. Anandamide (0.1-50 microg/50 microl) had inconsistent effects in non-inflamed rats. Following carrageenin inflammation, anandamide (50 microg/50 microl) significantly reduced evoked neuronal responses, C-fibre mediated non-potentiated and post-discharge responses of neurones reduced to 65 +/- 5% and 57 +/- 10% of control, respectively. Effects of anandamide were blocked by SR141716A, a selective CB1 receptor antagonist. Spinal SR141716A (0.001-1 ng/50 microl) alone did not influence neuronal responses in inflamed rats. Spinal anandamide inhibited nociceptive transmission via CB1 receptors; following inflammation there is evidence for a loss of spinal endogenous cannabinoid tone.

Animals↗
PubMed2000

Imidazoline I(2)-receptors and spinal reflexes in the decerebrated rabbit.

Idazoxan potentiates spinal reflexes in the decerebrated rabbit, an effect that has been attributed to antagonism of tonic noradrenergic inhibition. It is now known that this drug has a higher affinity for I(2)-imidazoline receptors than alpha(2)-receptors. The roles of I(2)-receptors in modulating transmission in spinal reflex pathways have been investigated using the selective ligands RX 821029 and RS-45041-190, and, as I(2)-receptors are closely associated with monoamine oxidase (MAO), the MAO inhibitors pargyline and clorgyline. In decerebrated rabbits with an intact spinal cord, intrathecal doses of 5-365 microg (cumulative) of the I(2)-ligands augmented, to 150-180% of pre-drug levels, the reflex responses of medial gastrocnemius motoneurones to electrical stimulation of the sural nerve, and significantly increased mean arterial blood pressure by approximately 10 mmHg over pre-drug values. Neither MAO inhibitor had significant effects on reflexes, but the highest dose of the MAO-A selective agent clorgyline (365 microg cumulative) caused a significant rise in blood pressure of 6 mmHg. Neither the I(2)-ligands nor the MAO inhibitors prevented the further enhancement of reflexes or blood pressure by subsequent administration of the selective alpha(2)-adrenoceptor antagonist RX 821002. In decerebrated, spinalized rabbits, intrathecal RS-45041-190 (60 microg, single dose) increased spinal reflex responses to 109% of pre-drug values, a significantly smaller effect than that seen in non-spinal preparations, and had no effect on blood pressure. These data show that imidazoline I(2)-receptors can influence somatic and autonomic motor outflows. These effects should be taken into account when interpreting the spinal effects of imidazoline-based adrenoceptor-active drugs.

Adrenergic alpha-Antagonists↗
PubMed2000

Reverse remodeling of cardiac myocyte hypertrophy in hypertension and failure by targeting of the renin-angiotensin system.

BACKGROUND: ACE inhibitors (ACEIs) and angiotensin II type 1 (AT(1)) receptor blockers are effective in reducing left ventricular mass in hypertension and heart failure. However, the ability of these drugs to reverse excessive myocyte lengthening and transverse growth in heart failure is unknown. METHODS AND RESULTS: L-158,809 (an AT(1) blocker; AT(1)), enalapril (an ACEI), and hydralazine (a vasodilator) were administered to spontaneously hypertensive heart failure rats between 6 and 10 months of age (early treatment) and between 18 and 22 months of age (late treatment). After 4 months of treatment, hemodynamics and chamber dimensions were collected before left ventricular myocyte isolation and subsequent analysis of myocyte shape. Each drug reduced systolic blood pressures to normal values. In the early and late studies, the ACEI reduced myocyte volume. Myocyte length was also reduced in the late study. However, the AT(1) was most effective in reversing myocyte dimensions to near-normal values in both studies. Hydralazine was ineffective in reducing cell size but arrested progression of myocyte lengthening in the late study. Changes in myocyte shape reflected alterations in chamber dimensions and wall thickness. CONCLUSIONS: Reversal of myocyte hypertrophy was produced in hypertensive/heart failure rats with an AT(1). The ACEI was effective but to a lesser extent. Results indicate that it is possible to significantly reverse myocyte remodeling pharmacologically even if therapy is initiated near the onset of failure. Further work is needed to determine whether similar results can be obtained in humans.

Angiotensin II↗
PubMed2000

Reduction of cardiac volume in left-breast treatment fields by respiratory maneuvers: a CT study.

PURPOSE: A previous study of healthy female volunteers suggested that deep inspiratory breath holding can reduce the cardiac volume in the treatment portals for left-breast cancer treatment. The reduction of irradiated cardiac volume may be important considering the reported late cardiac morbidity and mortality and the frequent coexistent use of potentially cardiotoxic chemotherapy in breast cancer patients. In the present study, we evaluated the heart volume in the fields and, thus, the true benefit of this respiratory maneuver in breast cancer patients undergoing CT simulation. MATERIALS AND METHODS: Fifteen patients (median age, 53) were studied. For each patient, CT scans were performed both when the patient breathed normally (quiet respiration) and when the patient held her breath after a deep inspiration. Tangential fields were planned using the same medial, lateral, superior, and inferior borders on skin for the normal breathing and the breath-holding configurations. The cardiac and left-lung volumes within the tangential fields were calculated for both breathing configurations. Multiple scan series were performed for the breath-holding configuration to provide a more accurate delineation of the cardiac tissue and to study the reproducibility of the patient's position between different cycles of deep inspiration. RESULTS: None of the patients had difficulty holding her breath for 20 s. The cardiac volume in the field was reduced (-86 +/- 24%; p < 0.001) when patients held their breath after a deep inspiration compared to when breathing normally. For 7 patients (47%), deep inspiration moved the heart completely out of the radiation fields. The expansion of the lung tissue due to deep inspiration also increased the absolute lung volume in the tangential fields (183 cm(3) vs 97 cm(3), p < 0.001). However, the fractional volume of the left lung in the field was essentially unchanged. For all but 1 patient, the maximum difference between the external body contours from different breath holding cycles was 5 mm and occurred at the lateral aspect of the breast. At the medial aspect, as indicated by the position of the midline marker, the variations were well within the currently accepted tolerance for patient positioning during tangential treatment. CONCLUSIONS: Deep-inspiration breath holding substantially reduces cardiac volume in the tangential fields for left-sided breast cancer treatment. The variation between patient positions at different cycles of breath holding was found to be reasonably small. Therefore, it appears feasible to reduce cardiac radiation by treating patients with intratreatment minifractions lasting 10-15 s while patients hold their breath.

Aged↗
PubMed2000

The Morphologies of the Small Magellanic Cloud.

We compare the distribution of stars of different spectral types, and hence mean age, within the central SMC and find that the asymmetric structures are almost exclusively composed of young main-sequence stars. Because of the relative lack of older stars in these features and the extremely regular distribution of red giant and clump stars in the SMC central body, we conclude that tides alone are not responsible for the irregular appearance of the central SMC. The dominant physical mechanism in determining the current-day appearance of the SMC must be star formation triggered by a hydrodynamic interaction between gaseous components. These results extend the results of population studies (see Gardiner & Hatzidimitriou) inward in radius and also confirm the suggestion of the spheroidal nature of the central SMC based on kinematic arguments (Dopita et al.; Hardy, Suntzeff, & Azzopardi). Finally, we find no evidence in the underlying older stellar population for a "bar" or "outer arm," again supporting our classification of the central SMC as a spheroidal body with highly irregular recent star formation.

Journal Article↗
PubMed2000

The gene for May-Hegglin anomaly localizes to a <1-Mb region on chromosome 22q12.3-13.1.

The May-Hegglin anomaly (MHA) is an autosomal dominant platelet disorder of unknown etiology. It is characterized by thrombocytopenia, giant platelets, and leukocyte inclusion bodies, and affected heterozygotes are predisposed to bleeding episodes. The MHA gene has recently been localized, by means of linkage analysis, to a 13.6-cM region on chromosome 22, and the complete chromosome 22 sequence has been reported. We recently performed a genome scan for the MHA gene in 29 members of a large, multigenerational Italian family, and we now confirm that the MHA locus is on chromosome 22q12. 3-13.1. The maximal two-point LOD score of 4.50 was achieved with the use of marker D22S283, at a recombination fraction of.05. Haplotype analysis narrowed the MHA critical region to 6.6 cM between markers D22S683 and D22S1177. It is of note that the chromosome 22 sequence allowed all markers to be ordered correctly, identified all the candidate genes and predicted genes, and specifically determined the physical size of the MHA region to be 0. 7 Mb. These results significantly narrow the region in which the MHA gene is located, and they represent the first use of chromosome 22 data to positionally clone a disease gene.

Blood Platelet Disorders↗
PubMed2000

Mental health. Facing hard truths.

A survey of 104 mental health units found that half did not have policies on treatment of detained patients from black and ethnic minority groups. Almost three-quarters had no policy for dealing with racial harassment of black and ethnic-minority patients. 11 percent of patients whose notes were examined had reported racial harassment.

Black or African American↗
PubMed2000

Anal sphincter conservation for patients with adenocarcinoma of the distal rectum: long-term results of radiation therapy oncology group protocol 89-02.

PURPOSE: To assess the outcome of a multi-institutional, national cooperative group study attempting functional preservation of the anorectum for patients with limited, distal rectal cancer. METHODS AND MATERIALS: Between September 21, 1989 and November 1, 1992, a Phase II trial of sphincter-sparing therapy was conducted for patients with clinically mobile rectal cancers located below the pelvic peritoneal reflection. Protocol treatment was designed for patients who were, in the judgement of their attending surgeon, unsuitable for anal sphincter conservation in the context of anterior resection, and would have required abdominoperineal resection (APR) as conventional surgical therapy. Primary cancers were estimated to be 4 cm or less in largest clinical diameter, and occupied 40% or less of the rectal circumference. Chest radiography and computerized axial tomography (CT) of the abdomen and pelvis excluded patients with overt lymphatic or hematogenous metastases. Protocol surgery was intended to remove the primary cancer by en-bloc, transmural excision of an ellipse of rectal wall by transanal, transcoccygeal, or trans-sacral technique, while conserving the anal sphincter. Based on tumor size, T classification, grade, and adequacy of surgical margins, patients were allocated to one of three treatment assignments: observation, or adjuvant treatment with 5-fluorouracil (5-FU) and one of two different dose levels of local-regional radiation. After completion of protocol therapy, patients were observed with follow-up that included periodic general physical and rectal examination, determinations of CEA, abdominopelvic CT, chest radiography, and surveillance endoscopy. Sixty-five eligible and analyzable patients were registered. RESULTS: With minimum follow-up of 5 years and median follow-up of 6.1 years, 11 patients have failed: 3 patients recurred local-regionally only, 3 patients had distant failure alone, and 5 patients manifested local-regional and distant failure. Eight patients died of intercurrent illness. Local-regional failure correlated with T-category revealed: T1 1/27 (4%), T2 4/25 (16%), and T3 3/13 (23%). Local-regional failure escalated with percentage involvement of the rectal circumference: 2/31 (6%) among patients with cancers involving 20% or less of the rectal circumference, and 6/34 (18%) among patients with cancers involving 21-40% of the circumference. Distant dissemination rose with T-category with 1/27 (4%) T1, 3/25 (12%) T2, and 4/13 (31%) T3 patients manifesting hematogenous spread. Eight patients (12%) required temporary or permanent colostomy. Five of 8 patients with local-regional recurrence achieved local-regional control with management including surgery, although 4 of these patients subsequently developed distant dissemination. Three patients (5%) had persistent, uncontrolled, local disease. Actuarial freedom from pelvic relapse at 5 years is 88% based on the entire study population, and 86% for the less favorable patients treated with adjuvant radiation and 5-FU. CONCLUSION: Conservative, sphincter-sparing therapy is a feasible alternative treatment for selected patients with limited cancer involving the middle and lower rectum. Risk of both local and distant failure appears to escalate with increasing T-category (depth of invasion). Results achieved in the multi-institutional, cooperative group setting approximate results reported from single institutions.

Adult↗
PubMed2000

Vecuronium pharmacokinetics and pharmacodynamics during hypothermic cardiopulmonary bypass in infants and children.

PURPOSE: To determine the effect of moderate and deep hypothermic cardiopulmonary bypass (CPB) on the pharmacokinetic and pharmacodynamic behaviour of vecuronium in infants and children. METHODS: We studied 12 patients undergoing surgery for congenital heart disease under narcotic-nitrous oxide anesthesia. Neuromuscular blockade was maintained constant (TI 4-10% by Datex electromyograph) by adjusting a vecuronium infusion. Plasma vecuronium concentrations (Cpss) were analysed by HPLC to describe a pseudosteady-state during each of the pre-CPB, CPB and post-CPB phases. Paired arterial blood samples were taken 20 min apart after at least 20 min of constant infusion. RESULTS: Nine cases were analysed, mean age 20 mo, mean weight 9 kg. Three patients had deep and six moderate hypothermia. In the pre-CPB phase Cpss fell into two groups (mean +/- SD: 330 +/- 42 ng x ml(-1); 127 +/- 27 ng x ml(-1); P < 0.001); similarly the clearances showed a bimodal distribution (mean +/- SD: 5.08 +/- 0.94; 11.51 +/- 0.2 ml x min(-1) x kg(-1) P < 0.001), although in different patients. During CPB this bimodal distribution disappeared. Vecuronium infusion rate (VIR) decreased by 84% and 92% from pre-CPB to CPB phase in deep and moderate hypothermia groups respectively (P < 0.05), paralleled by decreases in Cpss of 36% (P > 0.05) and 52% (P < 0.05). CONCLUSION: Changes in vecuronium requirements and plasma concentrations during CPB demonstrate that vecuronium pharmacokinetics and pharmacodynamics are both affected by hypothermic CPB in infants. The finding of bimodal distributions for plasma vecuronium and vecuronium clearance highlights the need for individual monitoring of neuromuscular blockade in this age group.

Anesthesia↗