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Biomedical subjects

J Deutsch

Publications and source records attributed to J Deutsch.

At least 73 records · Page 4Linked to original sources
PubMed1993

High glucose causes delayed fetal lung maturation as measured by fluorescence anisotropy.

Fluorescence anisotropy has been used to estimate the microviscosity of the surfactant phospholipid bilayer and no predict fetal lung maturity in human amniotic fluid; its usefulness in in vitro systems has been recently demonstrated. To investigate the effect of high glucose on lung development, anisotropy measurements were performed on 20-day fetal rat lung explant homogenates and culture media after culture for 48 hours in medium containing final concentrations of 10, 50, and 100mM glucose. Anisotropy of lung tissue cultured in 100mM glucose was significantly increased when compared to those cultured in 10mM glucose (p < .01). After 48 hours, the media from samples grown in 100mM glucose had significantly higher anisotropy (.2210 +/- .0031) than did media from explants grown in 50mM glucose (.2027 +/- .0079; p < .05), or in 10mM glucose (.1886 +/- .0046; p < .001). Relative fluorescence intensity of explants grown in 100mM glucose was 74.4 +/- 5.7% of those grown in 10mM glucose (p < .01). Fluorescence intensity of media was also decreased by 15-30% under higher glucose considerations (p < .05). These data suggest that surfactant synthesized and secreted under high glucose conditions, such as exist in the infant of the diabetic gestation, may have qualitative as well as quantitative changes.

Animals↗
PubMed1993

Development of lipophilic anticancer agents for the treatment of brain tumors by the esterification of water-soluble chlorambucil.

The lipophilic derivatives of the anticancer alkylating agent chlorambucil, chlorambucil-methyl, -isopropyl and -tertiary butyl esters, were synthesized and administered i.v. to anesthetized rats. Plasma and brain concentrations of these agents and of their active metabolites, chlorambucil and phenylacetic mustard, then were determined by high-performance liquid chromatography between 5 and 60 min. Whereas large amounts of chlorambucil-tertiary butyl ester entered and were maintained in brain, lower amounts of chlorambucil-isopropyl ester and no chlorambucil-methyl ester were found in brain. The comparative brain/plasma concentration-time integral ratios of the total active agents generated from chlorambucil-tertiary butyl, -isopropyl and -methyl esters were 0.85, 0.12 and 0.06, respectively, compared to a ratio of 0.02 for chlorambucil. In vitro alkylating activity of each ester was compared to that of equimolar chlorambucil, by reaction with 4-(p-nitrobenzyl)pyridine. Each ester possessed high intrinsic alkylating activity, equal to 38.4, 57.0 and 69.9% of chlorambucil activity, for the -tertiary butyl, -isopropyl and -methyl esters, respectively. Therefore each is an active antineoplastic agent irrespective of whether or not chlorambucil is regenerated. The rates of ester hydrolysis of these derivatives to chlorambucil were measured in fresh rat blood and in liver and brain homogenates at 37 degrees C. Chlorambucil-methyl and -isopropyl esters were hydrolysed quickly within 30 s in blood and liver, whereas chlorambucil-tertiary butyl ester was more stable with half-lives of approximately 7 h and 2 h, respectively. All proved to be relatively stable in brain homogenate. Steric hindrance around the ester linkage of chlorambucil-tertiary butyl ester reduces its affinity to and rate of hydrolysis by plasma and liver esterases, and allows it to accumulate within the brain. Chlorambucil-tertiary butyl ester maintains high levels in brain despite rapidly declining plasma concentrations and, due to these favorable pharmacokinetics and to its intrinsic anticancer activity, it possess promising characteristics for the treatment of malignant brain tumors.

Alkylating Agents↗
PubMed1993

In vivo functional characterization of an ecdysone response enhancer in the proximal upstream region of the Fbp1 gene of D. melanogaster.

Transcription of the D. melanogaster Fat-body-protein-1 (Fbp1) gene is induced by the steroid hormone 20-hydroxyecdysone and is restricted to the fat body tissue at the end of the third larval instar. The location and functional properties of the Fbp1 cis-acting regulatory sequences contained in the region from -1386 to +80 relative to the transcription start were examined by transformation using hybrid constructs with the Adh or lacZ genes as reporters. Regulatory element(s) required for the full level of transcription of the Fbp1 gene were located between positions -1386 and -138. Sequences between -138 and -68 were able to drive transcription from a heterologous minimal promoter in the fat body of late third instar larvae. Remarkably, these sequences also conferred 20-hydroxyecdysone inducibility and behaved as an enhancer-like element. These results provide the first functional characterization, at the level of the whole organism, using a direct in vivo ecdysone induction assay, of a discrete ecdysone response element.

Animals↗
PubMed1993

Comparison of the Keeler Pulsair 2000 non-contact tonometer with Goldmann applanation.

The Pulsair 2000 non-contact tonometer (Keeler Ltd, UK) is compared with the Goldmann applanation tonometer. Data from 80 eyes were acquired by four experienced observers. A linear regression analysis showed the relationship between the instruments to be: Pulsair = 0.66 + 0.95 Goldmann. Individual components of variation were analysed by analysis of variance which indicated a significant variation in the slope of the regression equation due to observers (p = 0.02) but not to the order in which topical anaesthesia was administered. Differences between two Pulsair instruments were of marginal significance (p = 0.07). The intercept of the regression equation was unaffected by any of the components of variation. Seventy-nine per cent of averaged intraocular pressure measurements obtained with the Pulsair 2000 fell on or within +/- 3 mmHg of those measured with the Goldmann tonometer. It is concluded that the Pulsair 2000 can provide clinically useful measurements of intraocular pressure.

Adolescent↗
PubMed1993

Deletion scanning of the regulatory sequences of the Fbp1 gene of Drosophila melanogaster using P transposase-induced deficiencies.

A procedure permitting deletion scanning of potential cis-regulatory sequences within a transgene whose genomic position remains fixed was applied to the study of the upstream sequences of the ecdysteroid-inducible Fat-body-protein-1 (Fbp1) gene. Deficiencies were induced in a Fbp1:Adh fusion transgene by means of a secondary P transposase mutagenesis. Phenotypic and molecular screens were used to select mutant transposons that retained their original genomic location and carried a deletion affecting the Fbp1 sequences but not the Adh reporter gene. Molecular mapping of the deletion breakpoints was achieved by sequence analysis and expression of the reporter gene was quantified by measurement of ADH activity. This procedure was efficient in detecting cis-acting elements, even those with moderate effects on levels of gene expression. For example, we have succeeded in identifying a negative regulatory element. Deletion of this element leads to a 50% increase in the reporter ADH activity. This element binds the transcription factor AEF-1. In addition, we have detected a strong, positively acting element contained within a 32-bp region located immediately upstream of an ecdysone-response element.

Alcohol Dehydrogenase↗
PubMed1993

Ocular manifestations of classical and limited Wegener's granulomatosis.

Wegener's granulomatosis (WG) may be subdivided into two forms, classical and limited. The latter specifically excludes renal disease and carries a better prognosis. Both forms have sight-threatening complications, but the relative incidence of ocular manifestations in each is not well documented. Patients with limited (n = 15) and classical (n = 16) WG were ophthalmologically examined. Ocular abnormalities found included orbital and nasolacrimal disease, corneo-scleral inflammation, dry eyes and retinal vein occlusion. In four patients (two from each group), no ocular disease was detected. The limited group included four potentially sight-threatening complications, compared to eight in the classical group. Overall, there was no statistically significant difference in any of the ocular manifestations between the two groups. Although treatment with corticosteroid and immunosuppressive agents has dramatically improved the prognosis of the disease, ocular morbidity is still well recognized. A combined medical and ophthalmological approach with prompt therapeutic intervention is recommended in these patients.

Adult↗
PubMed1992

Electron-impact and chemical ionization detection of nicotine and cotinine by gas chromatography-mass spectrometry in rat plasma and brain.

Nicotine and its metabolite, cotinine, were measured in rat plasma and brain by gas chromatography-mass spectrometry. Both agents were extracted from plasma and brain, separated on a capillary column, and quantified by single-ion monitoring. The major fragment ions of nicotine and cotinine at m/z 84 and m/z 98, respectively, were monitored by electron-impact ionization detection and the protonated molecular ions at m/z 163 and m/z 177, respectively, were monitored by chemical ionization detection. Both compounds were quantified using deuterium-labeled nicotine and cotinine, respectively, as internal standards.

Animals↗
PubMed1992

Red cell aplasia responsive to immunoglobulin therapy as initial manifestation of human immunodeficiency virus infection.

A patient who presented with pure red cell aplasia as the initial manifestation of human immunodeficiency infection is described. The patient had no signs of other autoimmune processes or immunologic or histologic evidence of parvovirus B19 infection, although we detected parvovirus B19 DNA in his serum. This patient had a complete, although temporary, response to a single course of immunoglobulin therapy and is currently responding to a second treatment.

Adult↗
PubMed1992

Removal of scleral explant elements: a 10-year retrospective study.

There are several studies in the American literature on the incidence and causes of retinal redetachment following removal of explants. This is, to our knowledge, the first such study from Britain and differs in its findings from the American experience. The reason for removal of explants, the time of removal after initial detachment surgery and the consequences of removal were reviewed for the 10-year period from 1980 to 1990. During this period 1898 retinal detachment operations were performed at this centre, with an explant removal rate of 3.2% (61 eyes). Extrusion of the element was the cause in 74%. Of these 8% subsequently suffered a redetachment. In two eyes no retinal break was identified at initial surgery. Both of these suffered a redetachment following removal of the explant. Contrary to previous reports, redetachment was not related to short periods of explant or to infection of the explant. This study suggests that explant removal is a safe procedure. However, there is a significant risk of redetachment after explant removal if no breaks are identified at the time of initial surgery.

Adolescent↗
PubMed1992

Myxoma mix-up. A case report.

We present a 63-year-old lady who had atrial myxoma. The diagnostic difficulties distinguishing this from giant cell arteritis are highlighted. In particular, both conditions caused choroidal and retinal infarcts, anterior ischaemic optic neuropathy, with raised acute phase reactants. The authors stress the importance of continued ophthalmoscopy as the fundal changes become more apparent.

Diagnosis, Differential↗
PubMed1991

Eyelid leishmaniasis in a patient with neurogenic ptosis.

A patient with chronic progressive external ophthalmoplegia contracted cutaneous leishmaniasis of the upper eyelid. Infection of this site is rare because eyelid movements usually prevent the sandfly vector from biting the skin there. It is postulated that the relative immobility of the upper eyelid in this patient was a major predisposing factor for the infection.

Antimony Sodium Gluconate↗
PubMed1991

Identification of 11,13-dihydroxy-14-octadecaenoic acid as a circulating Na+/K(+)-ATPase inhibitor.

Two digitalis-like compounds (DLC) were purified to homogeneity from bovine plasma. The purification procedure consisted of organic extractions and batch chromatography followed by three subsequent separations using reverse-phase high-performance liquid chromatography. The presence of a DLC in the different fractions was monitored by their ability to inhibit (a) [3H]ouabain binding to rat brain synaptosomes, and (b) microsomal Na+/K(+)-ATPase activity. Using mass spectrometry and nuclear magnetic resonance spectroscopy the structure of one of the DLCs was identified as 11,13-dihydroxy-14-octadecaenoic acid. It is suggested that this new hydroxy, unsaturated, fatty acid derivative may regulate Na+/K(+)-ATPase activity under some physiological and pathological conditions.

Animals↗
PubMed1990

Electron-impact ionization detection of scopolamine by gas chromatography-mass spectrometry in rat plasma and brain.

Scopolamine, a muscarinic receptor antagonist, was measured in rat plasma and brain using gas chromatography-mass spectrometry with electron-impact ionization detection. Extracted scopolamine was either directly derivatized or first hydrolyzed to scopine, then derivatized with heptafluorobutyric anhydride, separated on a capillary column and quantified by mass fragmentography. Electron-impact ionization produced a common fragment peak at m/z 138 that was monitored along with trideuterated scopolamine, an internal standard (m/z 141). The method can be used to measure scopolamine concentrations of 2 ng/ml in rat plasma and 20 ng/g in rat brain.

Animals↗
PubMed1990

Brain and plasma pharmacokinetics and anticancer activities of cyclophosphamide and phosphoramide mustard in the rat.

By a sensitive and quantitative fluorometric assay, brain and plasma time-dependent concentration profiles were generated for phosphoramide mustard (PM) and active alkylating metabolites derived from cyclophosphamide (CPA) administration to rats. Whereas PM rapidly disappeared from plasma, with a monophasic half-life of 15.1 min, equimolar administration of CPA generated active metabolites in plasma that disappeared monoexponentially, with a composite half-life of 63 min. As a consequence, the time-dependent concentration integral of active alkylating metabolites derived from CPA administration, calculated between 5 min and infinity, was 3-fold that of PM. Pharmacokinetic parameters were calculated for each compound. The brain/plasma concentration-integral ratios of PM and active alkylating metabolites derived from CPA were 0.18 and 0.20, respectively. The cerebrovascular permeability-surface area product of PM was 7.5 x 10(-5) s-1, which is similar to that of other water-soluble anticancer agents that are restricted from entering the brain. The activities of a range of daily doses of PM and CPA were assessed against subcutaneous and intracerebral implants of Walker 256 carcinosarcoma tumor in rats. Inhibition of subcutaneous tumor growth by 50% was caused by CPA and PM doses of 6.6 and 12.0 mg/kg (daily for 5 consecutive days, starting 36 h after tumor implantation), respectively. However, administration of daily doses of up to 40 mg/kg did not significantly increase the survival of animals with intracerebral tumor implants. These studies indicate that active metabolites of CPA are restricted from entering the brain and that only subtherapeutic concentrations are achieved in brain tissue after systemic administration of CPA or PM.

Animals↗