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Biomedical subjects

J Shepard

Publications and source records attributed to J Shepard.

At least 19 recordsLinked to original sources
PubMed2001

Stereotaxic delivery of corticosterone to the amygdala modulates colonic sensitivity in rats.

Episodes of anxiety are often associated with the onset or exacerbation of visceral pain in patients with irritable bowel syndrome (IBS). The central amygdaloid nucleus (CeA) is a key limbic structure involved in the expression of anxiety as well as a major site for regulating autonomic and visceral responses to stress. Previous experiments have shown that glucocorticoids can act directly at the CeA to increase the level of anxiety in rats. Therefore, the goal of this study was to examine the effect of stereotaxic delivery of corticosterone into the CeA on the development of visceral hypersensitivity by measuring visceromotor response to colorectal distention in rats. Stereotaxic delivery of corticosterone to the CeA increases indices of anxiety and produces a hypersensitive colon as demonstrated by an exaggerated visceromotor response to colorectal distention in the F344 rat strain. Our findings suggest that modulation of anxiety by manipulating amygdala function with corticosterone induced colonic hypersensitivity via descending neuronal pathways from the CeA.

Acetic Acid↗
PubMed2000

Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter.

Defects in iron absorption and utilization lead to iron deficiency and overload disorders. Adult mammals absorb iron through the duodenum, whereas embryos obtain iron through placental transport. Iron uptake from the intestinal lumen through the apical surface of polarized duodenal enterocytes is mediated by the divalent metal transporter, DMTi. A second transporter has been postulated to export iron across the basolateral surface to the circulation. Here we have used positional cloning to identify the gene responsible for the hypochromic anaemia of the zebrafish mutant weissherbst. The gene, ferroportin1, encodes a multiple-transmembrane domain protein, expressed in the yolk sac, that is a candidate for the elusive iron exporter. Zebrafish ferroportin1 is required for the transport of iron from maternally derived yolk stores to the circulation and functions as an iron exporter when expressed in Xenopus oocytes. Human Ferroportin1 is found at the basal surface of placental syncytiotrophoblasts, suggesting that it also transports iron from mother to embryo. Mammalian Ferroportin1 is expressed at the basolateral surface of duodenal enterocytes and could export cellular iron into the circulation. We propose that Ferroportin1 function may be perturbed in mammalian disorders of iron deficiency or overload.

Amino Acid Sequence↗
PubMed2000

An integrated genetic linkage map with 1,137 markers constructed from five F2 crosses of autoimmune disease-prone and -resistant inbred rat strains.

The rat (Rattus norvegicus) is an important experimental model for many human diseases including arthritis, diabetes, and other autoimmune and chronic inflammatory diseases. The rat genetic linkage map, however, is less well developed than those of mouse and human. Integrated rat genetic linkage maps have been previously reported by Pravenec et al. (1996, Mamm. Genome 7: 117-127) (500 markers mapped in one cross), Bihoreau et al. (1997, Genome Res. 7: 434-440) (767 markers mapped in three crosses), Wei et al. (1998, Mamm. Genome 9: 1002-1007) (562 markers mapped in two crosses), Brown et al. (1998, Mamm. Genome 9: 521-530) (678 markers mapped in four crosses), and Nordquist et al. (1999, Rat Genome 5: 15-20) (330 markers mapped in two crosses). The densest linkage map combined with a radiation hybrid map, reported by Steen et al. (1999, Genome Res. 9: AP1-AP8), includes 4736 markers mapped in two crosses. Here, we present an integrated linkage map with 1137 markers. We have constructed this map by genotyping F2 progeny of five crosses: F344/NHsd x LEW/NHsd (673 markers), DA/Bkl x F344/NHsd (531 markers), BN/SsN x LEW/N (714 markers), DA/Bkl x BN/SsNHsd (194 markers), and DA/Bkl x ACI/SegHsd (245 markers). These inbred rat strains vary in susceptibility/resistance to multiple autoimmune diseases and are used extensively for many types of investigation. The integrated map includes 360 loci mapped in three or more crosses. The map contains 196 new SSLP markers developed by our group, as well as many SSLP markers developed by other groups. Two hundred forty genes are incorporated in the map. This integrated map should allow comparison of rat genetic maps from different groups and thereby facilitate genetic studies of rat autoimmune and related disease models.

Animals↗
PubMed1997

Dysregulated proteolytic balance as the basis of excess extracellular matrix in fibrotic disease.

To investigate mechanisms of tissue fibrosis, we developed a model of ovine fetal bladder fibrosis due to surgically induced obstruction. Tissues were analyzed for matrix metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Active MMP-2 was not detected in obstructed bladders, while latent and active forms were detected in normal bladders. MMP-1 (interstitial collagenase) activity was lower in obstructed bladders. MMP inhibitory activity was increased with obstruction, as were levels of TIMP mRNA and protein. These results indicate that the proteins responsible for collagen degradation are present in the developing bladder, and a shift in the proteolytic balance favoring inhibition of degradation occurs in a model of obstruction-induced fibrosis. This altered proteolytic balance favors accumulation of extracellular matrix and decreased tissue compliance characteristic of this and perhaps other fibrotic conditions.

Animals↗
PubMed1994

Rapid assay of lactoferrin in keratoconjunctivitis sicca.

We compared measurement of lactoferrin concentration by the LactoCard solid phase ELISA assay with the LactoPlate radial immunodiffusion assay in tears of normal patients and those with keratoconjunctivitis sicca. The LactoCard, a new lactoferrin assay, allows rapid determination of tear lactoferrin concentration in 10-15 min, a notable improvement over the 3 days required of the LactoPlate. There was no statistically significant difference between the accuracy of the two assays in normal patients nor in those patients with a diagnosis of keratoconjunctivitis sicca. Both assays showed a significant decrease in tear lactoferrin concentration in patients with severe keratoconjunctivitis sicca when compared to normal patients. The LactoCard is a rapid and reliable means of measuring tear lactoferrin concentration in a clinical setting.

Adult↗
PubMed1993

Implantation in vivo and retrieval of artificial structures consisting of rabbit and human urothelium and human bladder muscle.

The harvest of human bladder muscle and urothelial cells with subsequent growth may be useful for tissue replacement in genitourinary reconstruction. We previously reported the development of a system for the harvest, delivery and growth of rabbit urothelium in vivo using biodegradable polymers. We have now expanded and adapted this system for the harvest and in vivo implantation of human bladder urothelial and muscle cells. Synthetic polymer fibers of polyglycolic acid can serve as a scaffold and a delivery vehicle for the implantation of rabbit uroepithelial cells into athymic host animals. The polymers, which slowly degrade in vivo, allow the urothelial cells to survive at the implant site. We demonstrate that polyglycolic acid polymers support the proliferation of rabbit urothelial cells in situ and can serve as a maleable substrate for the creation of new urological structures that replace the degrading polymer fibers. We also show that human urothelial cells and bladder muscle cells, when implanted on polyglycolic acid fibers, from new urological structures in vivo composed of both cell types. The human cell-polymer xenografts can be recovered from host animals at extended times after implantation. These data suggest that feasibility of using polyglycolic acid polymers as substrates for the creation of human urothelial and muscle grafts for genitourinary reconstruction.

Animals↗
PubMed1991

Effect of catheter size on pressures recorded in small pulmonary veins in dog lung.

Controversy continues about the contribution of the veins to pulmonary vascular resistance. From data obtained in studies using intravascular catheters, it appears that a major fraction (up to 44%) of the total pulmonary vascular pressure drop resides in larger (greater than 1.0 mm diam) veins, whereas micropuncture data and various models give much less pressure drop. Theoretically, artifactual pressure drops can be obtained if an intravascular catheter partly obstructs the vessel. We made measurements of pressure in the same lung vein with two different-sized catheters (1.2 and 0.6 mm OD, respectively). In paired experiments the larger catheter always measured a higher pressure than the smaller one, except close to the large lobar vein outlet. In some of the experiments we measured the diameter of the vessel containing the indwelling catheter by freezing the lung and then serial-sectioned the frozen lung. From these data we could infer that the range of vein diameter in the which the smaller catheter measured a lower pressure was 1.5-4 mm. We conclude that the larger catheter overestimated the pressure because of greater obstruction. The pressures obtained with the smaller catheter suggest that little (less than 10%) of the total pulmonary vascular resistance resides in veins larger than approximately 1 mm diam under zone 3 baseline conditions.

Animals↗
PubMed1990

A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome.

PURPOSE: Currently, there is no established therapy for chronic fatigue syndrome (CFS), a recently defined illness that has been associated with a variety of immunologic abnormalities. Based on the hypothesis that a chronic viral infection or an immunoregulatory defect is involved in the pathogenesis of CFS, the therapeutic benefit of intravenous immunoglobulin G (IV IgG) was evaluated in a group of patients with CFS. Additionally, serum immunoglobulin concentrations and peripheral blood lymphocyte subset numbers were measured at the outset of the study, and the effect of IV IgG therapy on IgG subclass levels was determined. PATIENTS AND METHODS: Thirty patients with CFS were enrolled in a double-blind, placebo-controlled trial of IV IgG. The treatment regimen consisted of IV IgG (1 g/kg) or intravenous placebo (1% albumin solution) administered every 30 days for 6 months. Participants completed a self-assessment form prior to each of the six treatments, which was used to measure severity of symptoms, functional status, and health perceptions. Patients were also asked to report adverse experiences defined as worsening of symptoms occurring within 48 hours of each treatment. RESULTS: Twenty-eight patients completed the trial. At baseline, all 28 patients complained of moderate to severe fatigue, and measures of social functioning and health perceptions showed marked impairment. Low levels of IgG1 were found in 12 (42.9%), and 18 (64.3%) had low levels of IgG3. At the end of the study, no significant therapeutic benefit could be detected in terms of symptom amelioration or improvement in functional status, despite restoration of IgG1 levels to a normal range. Major adverse experiences were observed in 20% of both the IV IgG and placebo groups. CONCLUSION: The results of this study indicate that IV IgG is unlikely to be of clinical benefit in CFS. In addition to the ongoing need for placebo-controlled trials of candidate therapies for CFS, an expanded research effort is needed to define the etiology and pathogenesis of this disorder.

Adult↗
PubMed1990

Multi-company working as one.

The consolidation of HR information processing in multi-union environments can result in significant cost savings; efficiencies in decision making; and flexibility to make changes.

Centralized Hospital Services↗
PubMed1987

No gravity-independent gradient of blood flow distribution in dog lung.

The existence of a major gravity-independent gradient of blood flow in lungs has recently been described based on single photon emission computed tomography after intravenous injection of radioactively labeled macroaggregates. We wanted to test this hypothesis of a major gravity-independent gradient in lung blood flow in experiments with direct measurement of macroaggregate distribution in the dog lung. In six anesthetized (4 prone spontaneously breathing, 2 mechanically ventilated) dogs we injected 111In-labeled albumin macroaggregates intravenously. We killed the dogs, removed, inflated, and froze the lower lobes. We sliced the lobes 1 cm thick and made gamma camera images of the slices. We then cut three or four slices in each lobe into two or three concentric layers and measured the radioactivity per gram of tissue in a well-type gamma counter. In three of the dogs we also labeled the red cells (99mTc) so that blood volume in each sample could be determined. The gamma camera images were acquired on a 64 X 64 matrix with 4 X 4 mm pixels. On the numeric printouts from the individual slices we made two or three concentric layers and calculated activity per pixel in each layer. Neither by the well counting nor by the pixel analysis of the gamma scans did we detect any gravity-independent distribution of blood flow. With the well counting the distribution was the same whether macroaggregate activity was expressed per gram of tissue or per gram of blood-free tissue. We conclude that by direct measurements no major gravity-independent gradient of pulmonary blood flow can be detected in dog lungs.

Animals↗
PubMed1980

Reducing hospitalizations of children with asthma.

This study sought to determine if the amount of in-hospital time could be reduced for a selected population of asthmatic children by using a behavioral intervention ("time-out" from positive reinforcement) in a general pediatric hospital. The measurements of hospital use selected were duration and frequency of hospitalization, and the time needed after admission to reverse airflow obstruction, as reflected by peak expiratory flow rates. Seven patients were selected because their use of the hospital appeared to be appreciably in excess of the severity of their asthma. All seven had been followed for at least one year prior to intervention, and were then followed for at least one year after the initial intervention. Intervention was a time-out procedure consisting of a program that removed many of the social rewards for being hospitalized. The results indicated that each of the measures of hospital use tested was reduced during and following the intervention.

Adolescent↗
PubMed1978

Reaction to phytotoxins in a potato population derived from mesophyll protoplasts.

Alternaria solani, the causal agent of early blight disease in potato, produces two host-specific, lipidlike toxins in culture. Both compounds are required in the leaf bioassay for the elicitation of typical early blight symptoms, but the compounds are individually inactive. The procedures for the preparation of both compounds are outlined. These compounds can be used effectively to select for toxin-insensitive and sensitive clones of a Russet Burbank potato cultivar that have been regenerated from single mesophyll protoplasts. Furthermore, both sensitivity and insensitivity to the toxins in these clones is well correlated with susceptibility and resistance to A. solani. Potato clones that have been produced by somatic cell regeneration techniques maintain their reaction type to these fungal toxins for at least two generations of vegetative propagation. The genetic basis for this variation among these potato clones remains to be explained.

Journal Article↗