Biomedical subjects

S Vogel

Publications and source records attributed to S Vogel.

At least 19 recordsLinked to original sources

PubMed2001

Characterization of a new member of the fatty acid-binding protein family that binds all-trans-retinol.

Cellular retinol-binding protein, type I (CRBP-I) and type II (CRBP-II) are the only members of the fatty acid-binding protein (FABP) family that process intracellular retinol. Heart and skeletal muscle take up postprandial retinol but express little or no CRBP-I or CRBP-II. We have identified an intracellular retinol-binding protein in these tissues. The 134-amino acid protein is encoded by a cDNA that is expressed primarily in heart, muscle and adipose tissue. It shares 57 and 56% sequence identity with CRBP-I and CRBP-II, respectively, but less than 40% with other members of the FABP family. In situ hybridization demonstrates that the protein is expressed at least as early as day 10 in developing heart and muscle tissue of the embryonic mouse. Fluorescence titrations of purified recombinant protein with retinol isomers indicates binding to all-trans-, 13-cis-, and 9-cis-retinol, with respective K(d) values of 109, 83, and 130 nm. Retinoic acids (all-trans-, 13-cis-, and 9-cis-), retinals (all-trans-, 13-cis-, and 9-cis-), fatty acids (laurate, myristate, palmitate, oleate, linoleate, arachidonate, and docosahexanoate), or fatty alcohols (palmityl, petrosenlinyl, and ricinolenyl) fail to bind. The distinct tissue expression pattern and binding specificity suggest that we have identified a novel FABP family member, cellular retinol-binding protein, type III.

Adipose Tissue↗

PubMed2001

Biochemical basis for depressed serum retinol levels in transthyretin-deficient mice.

Transthyretin (TTR) acts physiologically in the transport of retinol in the circulation. We previously reported the generation and partial characterization of TTR-deficient (TTR(-)) mice. TTR(-) mice have very low circulating levels of retinol and its specific transport protein, retinol-binding protein (RBP). We have examined the biochemical basis for the low plasma retinol-RBP levels. Cultured primary hepatocytes isolated from wild type (WT) and TTR(-) mice accumulated RBP in their media to an identical degree, suggesting that RBP was being secreted from the hepatocytes at the same rate. In vivo experiments support this conclusion. For the first 11 h after complete nephrectomy, the levels retinol and RBP rose in the circulations of WT and TTR(-) mice at nearly identical rates. However, human retinol-RBP injected intravenously was more rapidly cleared from the circulation (t(12) = 0.5 h for TTR(-) versus t(12) >6 h for WT) and accumulated faster in the kidneys of TTR(-) compared with WT mice. The rate of infiltration of the retinol-RBP complex from the circulation to tissue interstitial fluids was identical in both strains. Taken together, these data indicate that low circulating retinol-RBP levels in TTR(-) mice arise from increased renal filtration of the retinol-RBP complex.

Animals↗

PubMed2001

Interleukin-2 induced immune effects in human immunodeficiency virus-infected patients receiving intermittent interleukin-2 immunotherapy.

To characterize the immunological effects of intermittent IL-2 therapy, which leads to selective increases in CD4+ T lymphocytes in HIV-infected patients, 11 patients underwent extensive immunological evaluation. While IL-2 induced changes in both CD4+ and CD8+ cell number acutely, only CD4+ cells showed sustained increases following discontinuation of IL-2. Transient increases in expression of the activation markers CD38 and HLA-DR were seen on both CD4+ and CD8+ cells, but CD25 (a chain of the IL-2 receptor) increased exclusively on CD4+ cells. This increase in CD25 expression was sustained for months following discontinuation of IL-2, and was seen in naive as well as memory cells. IL-2 induced cell proliferation, but tachyphylaxis to these proliferative effects developed after 1 week despite continued IL-2 administration. It thus appears that sustained CD25 expression selectively on CD4+ cells is a critical component of the immunological response to IL-2, and that intermittent administration of IL-2 is necessary to overcome the tachyphylaxis to IL-2-induced proliferation.

ADP-ribosyl Cyclase↗

PubMed2001

Ethnic comparisons of disease severity in children hospitalized with pneumonia in New Zealand.

OBJECTIVE: To determine if there are ethnic differences in disease severity in children hospitalized with pneumonia in New Zealand. METHODOLOGY: A population based audit of children hospitalized in Auckland with pneumonia over 12 months from 1 November 1994 to 31 October 1995. The study population was children aged from 0 to 14 years with a discharge diagnosis of pneumonia. The sample was stratified by ethnicity and included 151 Pacific, 85 Mäori and 151 European children. Measurements were made of demographics and prehospital care; vital signs and therapy received in the emergency department and inpatient wards and laboratory investigations performed. Comparisons between the three ethnic groups were adjusted for age, weight, gender, socio-economic status and relationship with primary care. RESULTS: A larger proportion of Pacific (15%) and Mäori (22%) children than European children (8%) had a respiratory rate elevated for > or = 2 days, odds ratio (OR) (95% CI): Pacific versus European 2.7 (1.1, 6.8), Mäori versus European 4.3 (1.7, 11.6). A larger proportion of Pacific (15%) and Mäori (15%) children than European children (< 1%) had a heart rate elevated for > or = 2 days, OR Pacific versus European 17.2 (3.2, 320), Mäori versus European 26.1 (4.4, 508). Compared with European children, a larger proportion of Pacific and Mäori children received intravenous fluids and antibiotics. A larger proportion of Pacific (29%) and Mäori (27%) children than European children (11%) received oxygen for > = 2 days, OR Pacific versus European 3.2 (1.6, 6.6), Mäori versus Europeans 2.6 (1.2, 6.2). CONCLUSIONS: Based on the comparisons of vital signs and intensity of therapy, Pacific and Mäori children hospitalized with pneumonia have more severe pneumonia than European children.

Adolescent↗

PubMed2001

Signal integration in lipopolysaccharide (LPS)-stimulated murine macrophages.

Using a panel of LPS-inducible genes, selected for the capacity of their products to contribute to endotoxicity, normal macrophages were compared to macrophages deficient in CD14, CD11b/CD18, or TLR4 to elicit gene expression in response to Escherichia coli LPS or the LPS mimetic, Taxol. All genes were TLR4-dependent. At low doses of LPS or Taxol, all genes were also CD14-dependent; however, IP-10 and ICSBP remained poorly inducible even at much higher concentrations. A distinct subset of genes (COX-2, IL-12 p40, and IL-12 p35) was CD11b/CD18-dependent. NF-B translocation and MAPK phosphorylation were dysregulated in receptor-deficient macrophages. In contrast to E. coli LPS, a Porphyromonas gingivalis LPS preparation was found to be TLR2-, rather than TLR4-dependent, and resulted in differential expression of genes within the panel. These data suggest that: (i) TLR4 is necessary, but not sufficient, to induce the full repertoire of genes examined; (ii) CD14 and CD11b/CD18 facilitate signaling for induction of select subsets of genes that are also TLR4-dependent; and (iii) signaling through TLR2 versus TLR4 differs quantitatively/qualitatively. These data support an LPS signaling complex on murine macrophages that minimally includes CD14, CD11b/CD18, and TLR4 to respond to E. coli LPS to elicit the full spectrum of gene expression.

Animals↗

PubMed2000

Effects of intermittent interleukin-2 therapy on plasma and tissue human immunodeficiency virus levels and quasi-species expression.

To characterize the effects of intermittent interleukin (IL)-2 therapy on human immunodeficiency virus (HIV), 11 patients underwent detailed virological evaluation during a year of IL-2 therapy. Six patients showed a >0.5 log increase in plasma HIV during at least 1 IL-2 cycle, with 2 experiencing an increase in >50% of cycles. Three of the remaining 5 patients had a >0.5 log decrease during at least 1 IL-2 cycle, and the remaining patients exhibited <0.5 log changes. No changes in lymphoid (tonsil) levels of HIV were seen during the year. Quasi-species analysis in a separate cohort demonstrated that the virus induced by IL-2 most commonly resembled pre-IL-2 plasma quasi species. Thus, intermittent IL-2 does not result in sustained increases in either plasma or tissue levels of HIV and does not result in sustained expression of a previously silent quasi species.

Adult↗

PubMed2000

Some selective reactions of moenomycin A.

A number of new moenomycin A derivatives have been prepared. Their antibiotic properties highlight the very specific recognition of moenomycin A at the transglycosylase binding site which is the basis of the transglycosylase inhibiting property of moenomycin A (4a).

Anti-Bacterial Agents↗

PubMed2000

9-cis-retinoids: biosynthesis of 9-cis-retinoic acid.

Retinoids function through conformational alterations of ligand-dependent nuclear transcription factors, the retinoic acid receptors, and retinoid X receptors. 9-cis-Retinoic acid is a known biological ligand for retinoid X receptors, but its synthesis pathway in vivo is largely unknown. Recently, we identified a cis-retinol dehydrogenase (cRDH) that oxidizes 9-cis-retinol to 9-cis-retinal. Since both the expression of cRDH mRNA and its substrate are found in liver, we studied 9-cis-retinol metabolism and 9-cis-retinoic acid biosynthesis in two hepatic-derived cell types, Hep G2 hepatoma cells and HSC-T6 stellate cells. Both cell lines accumulate similar amounts of 9-cis-retinol provided in the medium. However, Hep G2 cells preferentially incorporate all-trans-retinol when equimolar concentrations of all-trans- and 9-cis-retinol were provided. In contrast, HSC-T6 cells did not exhibit a preference between all-trans- and 9-cis-retinol under the same conditions. Esterification of 9-cis-retinol occurred in both cell types, likely by acyl-CoA:retinol acyltransferase and lecithin:retinol acyltransferase. In vitro enzyme assays demonstrated that both cell types can hydrolyze 9-cis-retinyl esters via retinyl ester hydrolase(s). In Hep G2 cells, 9-cis-retinoic acid synthesis was strongly inhibited by high concentrations of 9-cis-retinol, which may explain the low levels of 9-cis-retinol in liver of mice. Cell homogenates of Hep G2 can convert all-trans-retinol to 9-cis-retinal, suggesting that the free form of all-trans-retinol may be used as a source for 9-cis-retinol and, thus, 9-cis-retinoic acid synthesis. Our studies provide the basis for identification of additional pathways for the generation of 9-cis-retinoic acid in specialized tissues.

Alcohol Oxidoreductases↗

PubMed2000

Pre-HAART HIV burden approximates post-HAART viral levels following interruption of therapy in patients with sustained viral suppression.

OBJECTIVE: To evaluate the relationship between the HIV viral burden in individuals prior to receiving highly-active antiretroviral therapy (HAART) and the viral burden after withdrawal of HAART. DESIGN AND SETTING: Retrospective cohort study at the National Institutes of Health, Bethesda, Maryland, USA. PATIENTS: Fourteen HIV-infected patients who achieved and maintained viral control on HAART who subsequently discontinued HAART. MAIN OUTCOME MEASURES: Pre- and post-HAART viral loads measured from plasma or serum. RESULTS: Patients achieved viral control (< 500 copies/ml) on HAART in a median 28 days (range, 15-490 days; mean, 72 days), maintained viral control for a median 661 days (range, 53-1067 days; mean, 611 days), and subsequently discontinued HAART for a median 49 days (range, 14-196 days; mean, 73 days). The median difference between the pre- and post-HAART viral loads was 0.16 log10 (range, -0.72 to 1.05 log10; mean, 0.19 log10). The median absolute difference between the pre- and post-HAART viral loads was 0.43 log10 (range, 0.06-1.05 log10; mean, 0.46 log10). Nine individuals had post-HAART values higher than pre-HAART values, five had lower values. Median duration between pre- and post-HAART viral load measurements was 1757 days (range, 117-3177 days; mean, 1756 days), or 4.8 years. CONCLUSIONS: After discontinuing HAART, individuals had rebounds in their viral burdens approximating pre-HAART levels, even after a significant lapse of time approaching 5 years. Our data suggest that an intrinsic viral load set-point may exist, and that a single interruption of an effective regimen with viral suppression for almost 2 years does not significantly alter this set-point.

Adult↗

PubMed2000

Cystic lesions of the pineal region--MRI and pathology.

Pineal lesions are rare. Tumours in this location comprise 0.4-1% of intracranial tumours. They grow mainly as solid-mass lesions, and cystic tumours are not common. On MRI, a cystic configuration is associated usually with non-neoplastic pineal lesions rather than with a tumour, but analysis does not allow cystic pineal tumours to be distinguished from glial cysts with certainty. We compared neuroradiological and pathological data from 13 cystic pineal lesions, analysing preoperative MRI. Formalin-fixed, paraffin-embedded surgical specimens were stained routinely and immunocytochemically, using the streptavidin-biotin-complex method. Histology revealed six pineocytomas, four glial cysts, an arachnoid cyst, a low-grade astrocytoma and a teratoma. Signal characteristics of pineocytomas were similar in many respects to those of glial pineal cysts. Histomorphological analysis allowed unambiguous discrimination between pineocytomas and glial pineal cysts.

Adolescent↗

PubMed2000

Diversity of mouse lipoxygenases: identification of a subfamily of epidermal isozymes exhibiting a differentiation-dependent mRNA expression pattern.

By using reverse transcription-polymerase chain reaction technology (RT-PCR) and Northern blot analysis, the tissue-specific mRNA expression patterns of seven mouse lipoxygenases (LOX)--including 5S-, 8S-, three isoforms of 12S-, 12R-LOX, and a LOX of an as-of-yet unknown specificity, epidermis-type LOX-3 (e-LOX-3)--were investigated in NMRI mice. Among the various tissues tested epidermis and forestomach were found to express the broadest spectrum of LOX. With the exception of 5S- and platelet-type 12S-LOX (p12S-LOX) the remaining LOX showed a preference to exclusive expression in stratifying epithelia of the mouse, in particular the integumental epidermis. The expression of the individual LOX in mouse epidermis was found to depend on the state of terminal differentiation of the keratinocytes. mRNA of epidermis-type 12S-LOX (e12S-LOX) was detected in all layers of neonatal and adult NMRI mouse skin, whereas expression of p12S-LOX, 12R-LOX, and e-LOX-3 was restricted to suprabasal epidermal layers of neonatal and adult mice. 8S-LOX mRNA showed a body-site-dependent expression in that it was detected in stratifying epithelia of footsole and forestomach but not in back skin epidermis. In the latter, 8S-LOX mRNA was strongly induced upon treatment with phorbol esters. With the exception of e12S-LOX and p12S-LOX, the isozymes that are preferentially expressed in stratifying epithelia are structurally related and may be grouped together into a distinct subgroup of epidermis-type LOX.

Aging↗

PubMed2000

Dietary cholesterol increases the susceptibility of low density lipoprotein to oxidative modification.

Evidence suggests that oxidative modification of low density lipoprotein (LDL) occurs in vivo, increasing the atherogenecity of the particle. A total of 13 subjects (age range 46-78 years) with an LDL cholesterol concentration >3.36 mmol/l consumed each of four diets for 32-day periods. The diets contained 30% energy as fat of which 2/3 was either corn oil or beef tallow with and without 115 mg/4.2 MJ of supplemental cholesterol in the form of cooked egg yolk. The susceptibility of LDL to oxidation was assessed during a challenge with hemin and hydrogen peroxide, and results are expressed as lag time to oxidation in minutes. Addition of moderate amounts of cholesterol to either the corn oil or beef tallow enriched diet resulted in increased susceptibility of LDL to oxidation (decreased lag time): 69+/-22 min versus 96+/-24 min in the corn oil diet with versus without supplemental cholesterol, respectively, P = 0.006; 82+/-20 min versus 96+/-26 min in the beef tallow diet with versus without supplemental cholesterol, respectively, P = 0.025. A stepwise equation indicated that as plasma oleic acid concentrations increased and/or linoleic acid concentrations decreased, lag time increased (decreased susceptibility to oxidation), whereas as dietary cholesterol concentrations increased, lag time decreased (increased susceptibility to oxidation). In conclusion, these data suggest that addition of a moderate amount of dietary cholesterol to a reduced fat diet rich in polyunsaturated or saturated fatty acids increased the in vitro susceptibility of LDL to oxidation.

Aged↗

PubMed2000

Pulmonary sequestration presenting as a prenatally detected suprarenal lesion in a neonate.

An echogenic suprarenal mass was detected antenatally in the fetus by routine ultrasound scan. Resection of the mass after delivery confirmed an extralobar pulmonary sequestration with features of a type II congenital cystic adenomatoid malformation of the lung. The lesion should be considered in all neonates presenting with a suprarenal or upper abdominal mass particularly when the mass has been detected antenatally. Ultrasound-guided needle biopsy if feasible could provide a reasonably confident diagnosis. Congenital anomalies in other organs should be looked for carefully.

Abdominal Neoplasms↗

PubMed2000

Patients' satisfaction with osteopathic and GP management of low back pain in the same surgery.

Chronic low back patients reported their satisfaction with the treatment they received for back pain from GPs and osteopaths practising in the same surgery. Although levels of satisfaction were high for all treatments, patients reported significantly higher scores for satisfaction with the osteopathic treatment. The difference was stronger for aspects of care/communication and competence, and weaker for satisfaction with efficacy. These findings are discussed in reference to patients' expectations, novelty, time spent with patients, number of visits, and patients' age.

Adult↗

PubMed2000

Combination therapy with amprenavir, abacavir, and efavirenz in human immunodeficiency virus (HIV)-infected patients failing a protease-inhibitor regimen: pharmacokinetic drug interactions and antiviral activity.

Patients with plasma viral RNA >50,000 copies/mL, despite a protease-inhibitor regimen, received abacavir, amprenavir, and efavirenz to assess efavirenz-amprenavir drug interactions and to evaluate safety and antiviral response. Patients first received amprenavir with abacavir and other nucleoside analogs. Amprenavir levels were measured before and after adding efavirenz. Patients then received a second protease inhibitor. There was evidence of genotypic and phenotypic resistance at study entry. No patient had study drugs discontinued because of toxicity. Efavirenz decreased the steady-state area under the curve, maximum plasma concentration, and minimum plasma concentration of amprenavir by 24%, 33%, and 43%, respectively. Three of 10 patients had >1.5 log10 viral response to abacavir and amprenavir. All 8 patients who added efavirenz had >0.5 log10 decline in viral load, and this response lasted >24 weeks for 3 of the patients. A combination regimen that included abacavir, amprenavir, and efavirenz was well tolerated and had sustained activity in some patients. Concomitant efavirenz therapy decreases amprenavir concentrations.

Adult↗

PubMed2000

Retinol and retinol-binding protein: gut integrity and circulating immunoglobulins.

Vitamin A (retinol) is required to maintain immunity and epithelial turnover and is a key micronutrient needed for combating infection. Vitamin A actions on the immune system are diverse and cannot be accounted for by a single effect or mechanism. The actions of retinol in maintaining gut integrity in humans and immunoglobulin levels in mice was investigated. For 30 children, performance on the lactulose/mannitol test, a test commonly used to assess intestinal barrier function, was inversely correlated (P=.012) with serum retinol concentrations. Thus, children with lower serum retinol, and presumably poorer vitamin A nutritional status, are more likely to have impaired intestinal integrity. Knockout mice that have impairments in plasma retinol transport have circulating immunoglobulin levels that are half those observed in matched wild type mice. No differences were observed in B and T cell populations present in spleen, thymus, and bone marrow.

Animals↗

PubMed2000

Augmented sympathetic response to bradykinin in the diabetic heart before autonomic denervation.

We studied whether diabetes mellitus affects the bradykinin (BK)-induced release of norepinephrine (NE) from rat cardiac sympathetic endings in situ. Three groups were studied. Group A (n=12) was rendered diabetic with streptozotocin (STZ), group B (n=13) received STZ and insulin, and group C (n=14) received citrate buffer only. NPH insulin was given to group B from day 7 after STZ. Atria were paced (3Hz) with rectangular voltage pulses at mechanical threshold intensity (0.15 V/cm). The release of NE was assessed through its effects on contractile force in the presence of atropine (1 micromol/L). Intensifying the field stimulation above the neural threshold ( approximately 0.4 V/cm) produced a graded positive inotropic effect that was due to the release of NE from sympathetic nerve endings. The additional effect of 0.1 micromol/L BK on the force of contraction was determined at half-maximal neural stimulation (ie, at approximately 0.65 V/cm). Then, after washing out BK and lowering the stimulation intensity to mechanical threshold, a cumulative dose-response curve for added NE was generated, allowing the positive inotropic effects of neural stimulation (with or without BK) to be expressed in terms of an equivalent inotropic concentration of added NE ([NE(eq)]). Neural stimulation, in the absence of BK, gave an [NE(eq)] of 32+/-3 nmol/L in group A, 44+/-6 nmol/L in group B, and 37+/-6 nmol/L in group C. BK increased [NE(eq)] by a factor of 6.2+/-0.9 in group A, 4.5+/-0.5 in group B, and 3.7+/-0.3 in group C. This factor was greater in group A than in group C but indistinguishable in groups B and C. Atria from normal and diabetic rats were incubated in (3)[H]NE for 60 minutes. Excess tracer was removed, and atria were stimulated during a series of 1-minute episodes at half-maximal neural stimulation to cause exocytotic (3)[H]NE release. BK augmented (3)[H]NE release in normal (n=4) and in diabetic (n=4) atria. This BK-induced increase of (3)[H]NE overflow (expressed as a fraction of tissue (3)[H]NE radioactivity) was 4 times greater in diabetic than in normal preparations. The response to BK in releasing sympathetic neurotransmitter is augmented in diabetic rats, recovering in a manner dependent on insulin.

Animals↗

PubMed2000

Reorientation of daffodil(Narcissus: Amaryllidaceae) flowers inwind: drag reduction andtorsional flexibility.

Daffodil flowers extend laterally from the long axes of their stems; as a result, wind on a flower exerts torsional as well as flexural stress on the stem. Stems respond by twisting, and thus flowers reorient to face downwind in moderate winds, in the process reducing their drag by ∼30%. This repositioning is facilitated by the stems' relatively low torsional stiffness. Daffodil stems have a ratio of flexural to torsional stiffness of 13.27 ± 0.96 (SD), compared with 8.33 ± 3.20 (SD) for tulip stems, which bear flowers as symmetrical extensions of their long axes, and compared with 1.5 for isotropic, incompressible, circular cylinders.

Journal Article↗