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Biomedical subjects

J Andrews

Publications and source records attributed to J Andrews.

At least 145 records · Page 8Linked to original sources

Ontogenesis of prolactin receptor gene expression in the rat olfactory system: potential roles for lactogenic hormones in olfactory development.

The PRL receptor (PRLR) is expressed at very low levels in the olfactory bulb of the adult rat but is detected in abundance in the olfactory epithelium and olfactory bulb of the fetal rat in late gestation. To explore potential roles for the lactogenic hormones in olfactory differentiation and development, we have used in situ hybridization and immunohistochemistry to examine the ontogeny of PRLR gene expression in the rat olfactory system. At midgestation (embryonic day 12.5), messenger RNAs (mRNAs) encoding the long and short isoforms of the rat PRLR were detected in the medial and lateral nasal processes, the epithelial lining of the olfactory pit, and the neuroepithelium lining the cerebral ventricles in the region of the rhinencephalon. PRLR mRNA was also expressed prominently in the frontonasal mesenchyme and in mesenchymal tissue underlying the developing brain and overlying the pontine flexure in the interpeduncular fossa. The distribution of PRLR immunoreactivity was similar to that of PRLR mRNA, indicating that the PRLR gene is translated to that of PRLR mRNA, indicating that the PRLR gene is translated to lactogenic binding protein in the rat embryo in vivo. With advancing gestation, the PRLR was expressed intensely, although discontinuously, in the olfactory epithelium and was detected in the cartilage primordia of the ethmoid, sphenoid, temporal, and mandibular bones. PRLR expression in the vomeronasal organ was confined to the luminal epithelial surface. PRLR mRNA and immunoreactive protein were first detected in the olfactory bulb on embryonic day 18. PRLR expression was most intense initially in the periventricular neuroepithelium; subsequently, robust staining of the mitral and tufted cell neurons became apparent, accompanied by intense PRLR expression in the sensory neuronal cell bodies of the olfactory epithelium. By postnatal day 5, the PRLR was expressed in abundance in mitral and tufted cells of the olfactory bulb and in neuronal cell bodies of the anterior olfactory nucleus and the piriform cortex. PRLR mRNA was also detected in the mitral cells of the olfactory bulb of the lactating rat, although at levels far lower than those in the fetal or neonatal rat. The expression of the PRLR in the olfactory system of the fetal and neonatal rat implicates novel roles for the lactogenic hormones in olfactory differentiation and development and may provide new mechanisms by which the lactogens may regulate neonatal behavior and maternal-infant interactions.

Animals↗

Predictability of designing specific binding interactions for DNA minor groove ligands from NMR spectroscopy and molecular modeling: a copper(II)-activated DNA cleaver based on Hoechst 33258.

Analogs of Hoechst 33258 have been designed and synthesized to incorporate a 3,4-catecholic or a 3,4,5-trihydroxyphenyl function in place of the 4-phenolic group of the template molecule. Molecular design was based on the three-dimensional models of the solution structures of the Hoechst 33258 and its m-hydroxy isomer which had been derived from high-field NMR spectroscopic analysis. The predicted solution structure of the catecholic analog as its minor groove complex with duplex d(CGCGAATTCGCG)2 was confirmed by direct high-resolution NMR spectroscopy combined with molecular dynamics, using NMR-derived distance restraints. While the 3,4-catecholic analog was unable to cleave DNA in the presence of Cu(II) ions, the 3,4,5-trihydroxyphenyl analog of Hoechst 33258 was found to be an effective cleaver of DNA at low concentration when activated by copper(II) ions, a difference ascribed to the inaccessibility for copper chelation of the 3,4-dihydroxy site in its minor groove complex with DNA.

Base Sequence↗

Tobacco prevention education in a pediatric residency program.

OBJECTIVE: To report the impact of a tobacco intervention in a pediatric residency program. DESIGN: Residents and faculty took pretests and posttests and follow-up surveys 6 months later. SETTING: An urban, university-affiliated, county medical center. INTERVENTION: An educational program of three presentations, written materials, and a bulletin board. RESULTS: Significant improvement in counseling and confidence in counseling. Perceptions of barriers to counseling, specifically expertise, time limitation, and doubts regarding counseling effectiveness diminished. Residents changed less than faculty in particular areas. There were no differences between the posttests and the follow-up survey 6 months later. CONCLUSIONS: Pediatric health professionals in an academic setting, given an educational program, will change their behaviors and attitudes about their role in counseling patients about tobacco use.

Adult↗

Cellular immunity in dogs with keratoconjunctivitis sicca before and after treatment with topical 2% cyclosporine.

Peripheral cellular immunity of ten dogs with keratoconjunctivitis sicca (KCS) that had not been treated with topical corticosteroids or cyclosporine was evaluated (by use of in vitro lymphocyte proliferation assays and CD4+/CD8+ lymphocyte subset analysis) before and after 1 and 3 months of treatment with topical ocular 2% cyclosporine (CsA). In vitro lymphocyte proliferation and CD4+/CD8+ lymphocyte subset analysis was done in eight normal dogs at the 0, 1 and 3 month time periods to use for comparison. There was no significant difference in lymphocyte proliferation or numbers of CD4+ or CD8+ lymphocytes in dogs with KCS and normal dogs prior to CsA treatment. However, by 1 month's time, lymphocyte proliferation had decreased in the CsA-treated Dogs with KCS, and by 3 months there was a significant difference (P < 0.0001) from the normal dogs. These results suggest that dogs with KCS may not have altered peripheral cellular immunity and that use of topical 2% cyclosporine for treatment of KCS causes a suppression of lymphocyte proliferation after 1 to 3 months of use.

Administration, Topical↗

The in-vitro activity of CP 99,219, a new naphthyridone antimicrobial agent: a comparison with fluoroquinolone agents.

The in-vitro activity of a new fluoroquinolone, CP 99,219 was compared with that of ciprofloxacin, DU 6859, sparfloxacin and levofloxacin. CP 99,219 showed generally similar in-vitro activity to the other compounds tested against the Enterobacteriaceae (MIC90 of all agents < 0.5 mg/L except Morganella morganii). It was found to be more active than ciprofloxacin, sparfloxacin and levofloxacin against the strains of Acinetobacter calcoaceticus tested (MIC90 1 mg/L). CP 99,219 was found to be four-fold more active against strains of Stenotrophomonas maltophilia than ciprofloxacin (MIC90 1 and 8 mg/L, respectively). Haemophilus influenzae and Neisseria spp. were highly susceptible to all the agents tested. CP 99,219 was more active than ciprofloxacin, sparfloxacin and levofloxacin against Gram-positive organisms, but less active than DU 6859. The enhanced anti-Gram-positive activity of CP 99,219 was most marked against the nine strains of methicillin-resistant Staphylococcus aureus tested. The MIC90 of CP 99,219 of these strains was 1.0 mg/L compared with 64 mg/L for ciprofloxacin. Against Bacteroides fragilis, CP 99,219 (MIC90 0.25 mg/L) and DU 6859 (MIC90 0.03 mg/L) were more active than the other quinolones. Chlamydia spp. were susceptible to < or = 0.12 mg/L of CP 99,219. Mycobacterial strains tested were less susceptible to CP 99,219 than to ciprofloxacin. The protein binding of CP 99,219 was 87.9% at 1 mg/L.

4-Quinolones↗

Inflammatory bowel disease--its history, current status and outlook.

In conclusion, it seems there has been a definite change in the epidemiology and course of IBD since earlier this century. Several points are worth emphasising: The diseases are relatively common, and there has been a general increase in their incidence, more so in some regions than others. The largest group affected is young adults, who will have their disease over several decades. This could potentially impact markedly on the workforce and on health care services. There is clearly a range of severity of this disease, and a greater number of mild cases have probably been diagnosed recently. This also helps to explain the differences in severity, need for surgery, and survival noted between community based studies and referral centre groups. Treatment has improved, particularly surgery (which usually takes place earlier on less critically ill patients), better operations, including continence surgery for most patients with UC and gut sparing procedures in Crohn's disease such as stricturoplasty. Medical management of acute disease has also improved which, in particular, has reduced mortality in elderly patients. Except for a subset of patients, life expectancy is close to normal, and time lost from the workforce, when considered in perspective over a working lifetime, is negligible. We can therefore be justifiably optimistic about the current long term outcome of IBD, and encourage our patients, their families and their employers to share in this outlook. With the promise of newer medical therapies on the horizon, prognosis may be further improved. Corticosteroids with little or no systemic side effects are currently in clinical trials and new anti-inflammatory agents are being examined for their efficacy through prostaglandin, leukotriene, or oxygen free-radical inhibition. Now that mortality from IBD is largely a thing of the past, we need to concentrate our attention more closely on the associated morbidity. It is to be hoped that future long term studies attempt the difficult clinical measurements of morbidity and quality of life.

Employment↗

An 1H NMR determination of the three-dimensional structures of mirror-image forms of a Leu-5 variant of the trypsin inhibitor from Ecballium elaterium (EETI-II).

The 3-dimensional structures of mirror-image forms of a Leu-5 variant of the trypsin inhibitor Ecballium elaterium (EETI-II) have been determined by 1H NMR spectroscopy and simulated annealing calculations incorporating NOE-derived distance constraints. Spectra were assigned using 2-dimensional NMR methods at 400 MHz, and internuclear distances were determined from NOESY experiments. Three-bond spin-spin couplings between C alpha H and amide protons, amide exchange rates, and the temperature dependence of amide chemical shifts were also measured. The structure consists largely of loops and turns, with a short region of beta-sheet. The Leu-5 substitution produces a substantial reduction in affinity for trypsin relative to native EETI-II, which contains an Ile at this position. The global structure of the Leu-5 analogue studied here is similar to that reported for native EETI-II (Heitz A, Chiche L, Le-Nguyen D, Castro B, 1989, Biochemistry 28:2392-2398) and to X-ray and NMR structures of the related proteinase inhibitor CMTI-I (Bode W et al., 1989, FEBS Lett 242:285-292; Holak TA et al., 1989a, J Mol Biol 210:649-654; Holak TA, Gondol D, Otlewski J, Wilusz T, 1989b, J Mol Biol 210:635-648; Holak TA, Habazettl J, Oschkinat H, Otlewski J, 1991, J Am Chem Soc 113:3196-3198). The region near the scissile bond is the most disordered part of the structure, based on geometric superimposition of 40 calculated structures. This disorder most likely reflects additional motion being present in this region relative to the rest of the protein. This motional disorder is increased in the Leu-5 analogue relative to the native form and may be responsible for its reduced trypsin binding. A second form of the protein synthesized with all (D) amino acids was also studied by NMR and found to have a spectrum identical with that of the (L) form. This is consistent with the (D) form being a mirror image of the (L) form and not distinguishable by NMR in an achiral solvent (i.e., H2O). The (D) form has no activity against trypsin, as would be expected for a mirror-image form.

Amino Acid Sequence↗

Directed movement of chromosome arms and fragments in mitotic newt lung cells using optical scissors and optical tweezers.

A pulsed-laser microbeam at 532 nm wavelength (optical scissors) and a laser-induced optical trap at 1064 nm wavelength (optical tweezers) have been successively combined to dissect and manipulate chromosomes in live newt lung epithelial cells. These preliminary experimental results demonstrated that chromosome fragments dissected by laser microbeam surgery, regardless of their size, could be easily pulled or rotated by optical forces when positioned at the periphery of the mitotic spindle. In addition, chromosome arms which were not subjected to laser microsurgery also could be moved with the optical tweezers at the spindle periphery. In our previous study on rat kangaroo kidney cells (PTK2), this degree of facilty in manipulating chromosome movement was not possible, most likely due to the close proximity of the intermediate filament "cage" to the spindle. It is concluded herein that optical scissors and tweezers can be used in combination to study the interaction of chromosomes with the mitotic spindle in cells where the peripheral regions of the spindle are unobstructed by intermediate filaments. This can be performed on newt cells, where the diameter of the cage can be substantially larger than the diameter of the spindle.

Animals↗

Biochemical differences (O-acetyl and glycolyl groups) in erythrocyte surface sialic acids of trypanotolerant N'dama and trypanosusceptible Zebu cattle.

Differences in the distribution and concentration of O-acetyl and glycolyl groups in erythrocyte sialic acids of trypanotolerant N'dama and trypanosusceptible Zebu cattle were investigated. Erythrocyte surface sialic acid concentrations were 25.4 +/- 5.5 mg per dl and 5.9 +/- 0.97 mg per dl in N'dama and Zebu animals, respectively. In N'damas, O-acetyl and glycolyl groups were present in concentrations of 16.4 +/- 4.3 mg per dl and 12.8 +/- 2.9 mg per dl, respectively, whereas the corresponding values in Zebus were 2.8 +/- 5.0 mg per dl and 7.6 +/- 1.7 mg per dl, respectively. The differences between N'dama and Zebu cattle in surface sialic acids and in O-acetyl and glycolyl groups were significant (P < 0.01 to < 0.001). N'dama erythrocyte sialic acids had more O-acetyl than glycolyl groups while those of Zebus had less O-acetyl than glycolyl groups. These findings may be relevant to the trypanotolerance of N'dama cattle.

Acetylation↗

Invasive zygomycosis due to Conidiobolus incongruus.

During the past decade, an increasing spectrum of pathogenic Zygomycetes fungi have caused infections in humans. The preponderance of these deeply invasive infections have been caused by members of the order Mucorales. However, deeply invasive zygomycoses due to genera of the order Entomophthorales (Conidiobolus species and Basidiobolus species) have seldom been reported. We describe a granulocytopenic patient with pulmonary and pericardial zygomycosis due to Conidiobolus incongruus, describe this organism's susceptibility to antifungal agents, characterize its diagnostic microbiological characteristics, and review previously reported cases of deeply invasive zygomycosis due to Conidiobolus species. In immunocompromised patients, C. incongruus is an uncommon but highly invasive fungal pathogen that may be resistant to amphotericin B and can be distinguished from other Zygomycetes fungi by characteristic mycological features.

Adult↗