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Biomedical subjects

S M Jones

Publications and source records attributed to S M Jones.

At least 73 records · Page 4Linked to original sources
PubMed1998

Role of dynamin in the formation of transport vesicles from the trans-Golgi network.

Dynamin guanosine triphosphatases support the scission of clathrin-coated vesicles from the plasmalemma during endocytosis. By fluorescence microscopy of cultured rat hepatocytes, a green fluorescent protein-dynamin II fusion protein localized with clathrin-coated vesicles at the Golgi complex. A cell-free assay was utilized to demonstrate the role of dynamin in vesicle formation at the trans-Golgi. Addition of peptide-specific anti-dynamin antibodies to the assay mixture inhibited both constitutive exocytic and clathrin-coated vesicle formation. Immunodepletion of dynamin proteins also inhibited vesicle formation, and budding efficiency was restored upon readdition of purified dynamin. These data suggest that dynamin participates in the formation of distinct transport vesicles from the trans-Golgi network.

Adenosine Triphosphate↗
PubMed1998

A novel BRCA1 mutation in an identical twin pair with similar clinical histories.

Factors affecting the penetrance and expression of BRCA1 are not understood. Breast cancer risk and ovarian cancer risk, in general, are known to be associated with non-Mendelian factors. However, whether and how these various factors influence tumor development in BRCA1 mutation carriers is not known. Here we report the breast and ovarian cancer syndrome in an identical twin pair. These female identical twins had remarkably similar clinical histories. Both twins developed histologically similar ovarian cancer in their mid-fifties. One twin was diagnosed with stage III disease and died of refractory metastatic disease. The other twin was diagnosed with stage I disease but ultimately died of recurrent disease. Neither twin developed breast or colon cancer. The twins have both similarities and differences in terms of nongenetic cancer-related risk factors. Results of BRCA1 analysis of DNA from both twins revealed a novel mutation, 2711delA, which resulted in a premature termination at codon 892. This report has intriguing implications concerning the role of genotype in the ultimate penetrance and expression of disease among BRCA1 mutation carriers.

Breast Neoplasms↗
PubMed1998

Dietary juniper berry oil minimizes hepatic reperfusion injury in the rat.

Juniper berry oil is rich in 5,11,14-eicosatrienoic acid, a polyunsaturated fatty acid similar to one found in fish oil, yet less prone to peroxidation. Dietary fish oil treatment has been shown to effectively reduce reperfusion injury; therefore, the effects of a diet containing juniper berry oil on hepatic reperfusion injury in a low-flow, reflow reperfusion model were investigated in the rat. Rats were fed semisynthetic diets containing either juniper berry oil, fish oil, or corn oil for 14 to 16 days. Daily food consumption averaged around 20 g/d in both the control and treatment groups; average daily weight gain was around 4 g per 100 g rat weight in all three groups studied, and there were no significant differences in these parameters. Livers were initially perfused at low-flow rates to induce pericentral hypoxia followed by a 40-minute reperfusion period. Peak lactate dehydrogenase (LDH) release during reflow averaged 44 U/g/h in the corn oil group and 32 U/g/h in the fish oil group, but was only 21 U/g/h as a result of juniper berry oil treatment. Malondialdehyde (MDA), an end-product of lipid peroxidation, reached a maximum value of 62 nmol/g/h in the corn oil group, but only reached 43 nmol/g/h and 34 nmol/g/h in the fish oil and juniper berry oil groups, respectively. Both juniper berry oil and fish oil treatment improved rates of bile flow from 25 microL/g/h (corn oil) to 36 and 38 microL/g/h, respectively. Importantly, juniper berry oil reduced cell death in pericentral regions of the liver lobule by 75%. Trypan blue distribution time, an indicator of the hepatic microcirculation, was reduced by approximately 25% with fish oil and over 50% by juniper berry oil diets compared with corn oil controls. The rates of entry of fluorescein-dextran, a dye confined to the vascular space, were increased 1.8- and 2.6-fold, and rates of outflow were increased 4.4- and 4.3-fold by fish oil and juniper berry oil, respectively, also reflecting improved microcirculation. Juniper berry oil also blunted increases in intracellular calcium and release of prostaglandin E2 (PGE2) by cultured Kupffer cells stimulated by endotoxin. These results are consistent with the hypothesis that feeding a diet containing juniper berry oil reduces reperfusion injury by inhibiting activation of Kupffer cells, thus reducing vasoactive eicosanoid release and improving the hepatic microcirculation in livers undergoing oxidant stress.

Animal Feed↗
PubMed1998

Atopic dermatitis and food hypersensitivity reactions.

OBJECTIVE: To determine the role of food hypersensitivity in atopic dermatitis and to determine whether patients with atopic dermatitis who had food hypersensitivity could be identified by screening prick skin tests using a limited number of food allergens. STUDY DESIGN: Patients with atopic dermatitis attending the Arkansas Children's Hospital Pediatric Allergy Clinic underwent allergy prick skin testing to a battery of food antigens. Patients with positive prick skin tests underwent double-blind, placebo-controlled food challenges. RESULTS: One-hundred sixty-five patients were enrolled and completed the study. Patients ranged in age from 4 months to 21.9 years (mean 48.9 months). Ninety-eight (60%) patients had at least one positive prick skin test. A total of 266 double-blind, placebo-controlled food challenges were performed. Sixty-four patients (38.7% of total) were interpreted as having a positive challenge. Seven foods (milk, egg, peanut, soy, wheat, cod/catfish, cashew) accounted for 89% of the positive challenges. By use of screening prick skin tests for these seven foods we could identify 99% of the food allergic patients correctly. CONCLUSIONS: This study confirms that most children with atopic dermatitis have food allergy that can be diagnosed by a prick skin test for the seven foods.

Adolescent↗
PubMed1998

Vestibular function in Belgian Waterslager canaries (Serinus canarius).

The purpose of this study was to measure vestibular function in Belgian Waterslager canaries using short latency vestibular evoked potentials (VsEPs) elicited by linear acceleration stimuli. Responses were recorded with vertex to mastoid leads using traditional signal averaging. Response thresholds, latencies, and amplitudes were quantified and compared to non-Waterslager controls. Cochlear and vestibular organs were also processed for scanning electron microscopy. Results indicated that vestibular response thresholds were slightly, but significantly, higher for Belgian Waterslager canaries and response amplitudes at 0 dBre: 1.0 g/ms were significantly reduced compared to non-Waterslagers. Response peak latencies were not significantly different. The most striking morphological finding was that the stereociliary bundles of Waterslager saccular hair cells showed no common orientation. Previous reports have also found significantly less hair cells in Waterslager saccules (Weisleder and Park, Hear. Res. 80 (1994) 64-70); however, the present study did not confirm this finding. The utricle and ampullae appeared normal. The present results indicate that vestibular neural function, as measured with VsEPs, is affected in Belgian Waterslager canaries. The results also suggest that one structural correlate of the functional loss is the disordered stereociliary bundles in the sacculus.

Acoustic Stimulation↗
PubMed1998

Resolving conflict creatively: evaluating the developmental effects of a school-based violence prevention program in neighborhood and classroom context.

This study evaluated the short-term impact of a school-based violence prevention initiative on developmental processes thought to place children at risk for future aggression and violence and examined the influence of classroom and neighborhood contexts on the effectiveness of the violence prevention initiative. Two waves of developmental data (fall and spring) were analyzed from the 1st year of the evaluation of the Resolving Conflict Creatively Program (RCCP), which includes 5053 children from grades two to six from 11 elementary schools in New York City. Three distinct profiles of exposure to the intervention were derived from Management Information System (MIS) data on between classroom differences in teacher Training and Coaching in RCCP, Classroom Instruction in RCCP, and percentages of students who are Peer Mediators. Developmental processes that place children at risk were found to increase over the course of the school year. Children whose teachers had a moderate amount of training and coaching from RCCP and who taught many lessons showed significantly slower growth in aggression-related processes, and less of a decrease in competence-related processes, compared to children whose teachers taught few or no lessons. Contrary to expectation, children whose teachers had a higher level of training and coaching in the RCCP but taught few lessons showed significantly faster growth over time in aggressive cognitions and behaviors. The impact of the intervention on children's social cognitions (but not on their interpersonal behaviors) varied by context. Specifically the positive effect of High Lessons was dampened for children in high-risk classrooms and neighborhoods. Implications for future research on developmental psychopathology in context and for the design of preventive interventions are discussed.

Achievement↗
PubMed1998

Macromolecular organisation of recombinant Yersinia pestis F1 antigen and the effect of structure on immunogenicity.

Yersinia pestis, the causative organism of plague, produces a capsular protein (fraction 1 or F1 antigen) that is one of the major virulence factors of the bacterium. We report here the production, structural and immunological characterisation of a recombinant F1 antigen (rF1). The rF1 was purified by ammonium sulfate fractionation followed by FPLC Superose gel filtration chromatography. Using FPLC gel filtration chromatography and capillary electrophoresis, we have demonstrated that rF1 antigen exists as a multimer of high molecular mass. This multimer dissociates after heating in the presence of SDS and reassociation occurs upon the removal of SDS. Using circular dichroism, we have monitored the reassociation of monomeric rF1 into a multimeric form. Mice immunised with monomeric or multimeric rF1 develop similar immune responses, but mice immunised with monomeric rF1 were significantly less well protected against a challenge of 1 x 10(6) cfu of Y. pestis than mice immunised with multimeric rF1 (1/7 compared with 5/7). The significance of this result in terms of the structure and the function of rF1 is discussed.

Animals↗
PubMed1997

Phosphatidylinositol 3-kinase is required for the formation of constitutive transport vesicles from the TGN.

An 85-kD cytosolic complex (p62(cplx)), consisting of a 62-kD phosphoprotein (p62) and a 25-kD GTPase, has been shown to be essential for the cell-free reconstitution of polymeric IgA receptor (pIgA-R)-containing exocytic transport vesicle formation from the TGN (Jones, S.M., J.R. Crosby, J. Salamero, and K.E. Howell. 1993. J. Cell Biol. 122:775-788). Here the p62(cplx) is identified as a regulatory subunit of a novel phosphatidylinositol 3-kinase (PI3-kinase). This p62(cplx)-associated PI3-kinase activity is stimulated by activation of the p62(cplx)-associated GTPase, and is specific for phosphatidylinositol (PI) as substrate, and is sensitive to wortmannin at micromolar concentrations. The direct role of this p62(cplx)-associated PI3-kinase activity in TGN-derived vesicle formation is indicated by the finding that both lipid kinase activity and the formation of pIgA-R-containing exocytic vesicles from the TGN are inhibited by wortmannin with similar dose-response curves and 50% inhibitory concentrations (3.5 microM). These findings indicate that phosphatidylinositol-3-phosphate (PI[3]P) is required for the formation of TGN-derived exocytic transport vesicles, and that the p62(cplx)-associated PI3-kinase and an activated GTPase are the essential molecules that drive production of this PI(3)P.

Amino Acid Sequence↗
PubMed1997

Two-dimensional mapping of the endogenous proteins of the rat hepatocyte Golgi complex cleared of proteins in transit.

The discovery of additional endogenous Golgi proteins will lead to significant new insights into Golgi function. To this end, stacked Golgi fractions (SGFs) were isolated from rat liver before (CTL SGF) and after molecules in transit through the Golgi were cleared by pre-treatment with cycloheximide (CHX SGF). Electron microscopic (EM) morphometric and biochemical analyses showed that the in vivo stacked morphology is retained, that > 90% of the elements can be positively identified as Golgi stacks and cisternae, and that transmembrane protein markers of the Golgi complex are enriched 300- to 800-fold over starting postnuclear supernatant (PNS). High-resolution two-dimensional (2-D) gel mapping has been carried out on the CTL PNS, CTL SII (an intermediate fraction), CTL SGF, CHX SGF, CHX SGF - high pH supernatant, and CHX SGF - high pH pellet. This analysis, coupled with immunoblotting and alignment of the 2-D gels with master gels, has allowed the identification of a number of known proteins and the preliminary characterization of the most abundant 173 Golgi-specific proteins. These 173 proteins have been placed into three categories: cargo, cytosolic Golgi-associated, and resident Golgi proteins. These categories are tentative and will be modified as more data are acquired from immunoblotting and protein sequencing.

Animals↗
PubMed1997

Asynchronous male and female gonadal cycles and plasma steroid concentrations in a viviparous lizard, Niveoscincus ocellatus (Scincidae), from Tasmania.

The reproductive cycle in males of the skink, Niveoscincus ocellatus, is characterised by testicular development during summer, followed by mating in autumn. Plasma testosterone concentrations show a bimodal seasonal cycle, with the major peak (18.6 +/- 1.2 ng/ml) in late summer/autumn and a minor peak (7.4 +/- 1.0 ng/ml) at spring emergence. In contrast to the males, the females have a gonadal cycle in which mating is temporally dissociated from peak development of the gonads: ovulation occurs in spring and the young are born in summer. Fresh mating marks on females in spring indicate that at least part of the population mates for a second time after spring emergence. In females, plasma estradiol concentrations are significantly elevated (956 +/- 214 pg/ml) through vitellogenesis and are highest (1241 +/- 175 pg/ml) during the preovulatory phase. Plasma progesterone concentrations rise during gestation to 6.5 +/- 1.5 ng/ml, but fall in the final stage of gestation to 1.6 +/- 0.2 ng/ml. There is minimal atresia of vitellogenic follicles, suggesting that clutch size is determined when the follicles are recruited for vitellogenesis.

Animals↗
PubMed1997

Short latency vestibular evoked potentials in the Japanese quail (Coturnix coturnix japonica).

Short-latency vestibular-evoked potentials to pulsed linear acceleration were characterized in the quail. Responses occurred within 8 ms following the onset of stimuli and were composed of a series of positive and negative peaks. The latencies and amplitudes of the first four peaks were quantitatively characterized. Mean latencies at 1.0 g ms-1 ranged from 1265 +/- 208 microseconds (P1, N = 18) to 4802 +/- 441 microseconds (N4, N = 13). Amplitudes ranged from 3.72 +/- 1.51 microV (P1/N1, N = 18) to 1.49 +/- 0.77 microV (P3/N3, N = 16). Latency-intensity (LI) slopes ranged from -38.7 +/- 7.3 microseconds dB-1 (P1, N = 18) to -71.6 +/- 21.9 microseconds dB-1 (N3, N = 15) and amplitude-intensity (AI) slopes ranged from 0.20 +/- 0.08 microV dB-1 (P1/N1, N = 18) to 0.07 +/- 0.04 microV dB-1 (P3/N3, N = 11). The mean response threshold across all animals was -21.83 +/- 3.34 dB re: 1.0 g ms-1 (N = 18). Responses remained after cochlear extirpation showing that they could not depend critically on cochlear activity. Responses were eliminated by destruction of the vestibular end organs, thus showing that responses depended critically and specifically on the vestibular system. The results demonstrate that the responses are vestibular and the findings provide a scientific basis for using vestibular responses to evaluate vestibular function through ontogeny and senescence in the quail.

Animals↗
PubMed1997

Usefulness of cytopathology and histology in the evaluation of Barrett's esophagus in a community hospital.

BACKGROUND: Brush cytology and histology have been found to be complementary in the evaluation of Barrett's esophagus at a referral medical center. This study evaluated the usefulness of brush cytology and histology in a community hospital setting. METHODS: One hundred consecutive patients with Barrett's esophagus underwent esophagogastroscopy performed by four staff gastroenterologists. Four quadrant biopsy specimens for histopathology at 3-cm intervals throughout the Barrett's segment and one brushing for cytology were obtained. All specimens were interpreted by four board-certified staff pathologists in a blinded fashion. RESULTS: Histologic diagnosis included three adenocarcinomas, one high-grade dysplasia, six low-grade dysplasias, and one indeterminate dysplasia. Cytology diagnosed the same three adenocarcinomas, no high-grade dysplasia, three low-grade dysplasia, and two indeterminate dysplasias. The case of high-grade dysplasia on histology was diagnosed as normal by cytology. The six patients found to have low-grade dysplasia by histology were found to have low-grade dysplasia (3), indeterminate dysplasia (2), and no abnormality (1) by cytology. In no case was a higher grade of dysplasia diagnosed by cytology than by histology. CONCLUSION: Adding brush cytology to histology increased the cost but not the diagnostic yield in the evaluation of Barrett's esophagus in a community hospital setting.

Adenocarcinoma↗
PubMed1997

Open carpal tunnel release. Does a vascularized hypothenar fat pad reduce wound tenderness?

Carpal tunnel decompression gives relief of symptoms of tingling and numbness in the fingers in around 90% of carpal tunnel syndrome cases. The most common complaint after operation is pain and tenderness about the operation scar. The normal median nerve slides back and forth during wrist movement. Loss of this movement due to scar adhesion is suggested as a cause of wound pain and residual symptoms. We performed a controlled, blinded study of bilateral primary carpal tunnel releases comparing standard closure with a hypothenar fat pad flap modified closure. No significant differences in pain or other symptoms were found.

Adipose Tissue↗
PubMed1997

Characterization of the Golgi complex cleared of proteins in transit and examination of calcium uptake activities.

To characterize endogenous molecules and activities of the Golgi complex, proteins in transit were > 99% cleared from rat hepatocytes by using cycloheximide (CHX) treatment. The loss of proteins in transit resulted in condensation of the Golgi cisternae and stacks. Isolation of a stacked Golgi fraction is equally efficient with or without proteins in transit [control (CTL SGF1) and cycloheximide (CHX SGF1)]. Electron microscopy and morphometric analysis showed that > 90% of the elements could be positively identified as Golgi stacks or cisternae. Biochemical analysis showed that the cis-, medial-, trans-, and TGN Golgi markers were enriched over the postnuclear supernatant 200- to 400-fold with and 400- to 700-fold without proteins in transit. To provide information on a mechanism for import of calcium required at the later stages of the secretory pathway, calcium uptake into CTL SGF1 and CHX SGF1 was examined. All calcium uptake into CTL SGF1 was dependent on a thapsigargin-resistant pump not resident to the Golgi complex and a thapsigargin-sensitive pump resident to the Golgi. Experiments using CHX SGF1 showed that the thapsigargin-resistant activity was a plasma membrane calcium ATPase isoform in transit to the plasma membrane and the thapsigargin-sensitive pump was a sarcoplasmic/endoplasmic reticulum calcium ATPase isoform. In vivo both of these calcium ATPases function to maintain millimolar levels of calcium within the Golgi lumen.

Adenosine Triphosphatases↗