Search PubMed⌕ Search

Biomedical subjects

M Schwartzman

Publications and source records attributed to M Schwartzman.

At least 19 recordsLinked to original sources
PubMed2001

Human heme oxygenase-1 gene transfer lowers blood pressure and promotes growth in spontaneously hypertensive rats.

Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, with release of free iron and carbon monoxide. Both heme and carbon monoxide have been implicated in the regulation of vascular tone. A retroviral vector containing human HO-1 cDNA (LSN-HHO-1) was constructed and subjected to purification and concentration of the viral particles to achieve 5x10(9) to 1x10(10) colony-forming units per milliliter. The ability of concentrated infectious viral particles to express human HO-1 (HHO-1) in vivo was tested. A single intracardiac injection of the concentrated infectious viral particles (expressing HHO-1) to 5-day-old spontaneously hypertensive rats resulted in functional expression of the HHO-1 gene and attenuation of the development of hypertension. Rats expressing HHO-1 showed a significant decrease in urinary excretion of a vasoconstrictor arachidonic acid metabolite and a reduction in myogenic responses to increased intraluminal pressure in isolated arterioles. Unexpectedly, HHO-1 chimeric rats showed a simultaneous significant proportionate increase in somatic growth. Thus, delivery of HHO-1 gene by retroviral vector attenuates the development of hypertension and promotes body growth in spontaneously hypertensive rats.

Animals↗
PubMed2000

Selective inhibition of arachidonic acid epoxidation in vivo.

Cytochrome P450 (CYP)-derived arachidonic acid metabolites, including epoxyeicosatrienoic acids (EETS) and 20-HETE, have been implicated in the regulation of renal function and vascular tone. Studying the function of specific CYP arachidonate metabolites has been hampered due to lack of selective inhibitors and difficulty in their solubilization. We have identified MS-PPOH as a potent and selective inhibitor of CYP-catalyzed arachidonate epoxidation in vitro. We used 2-hydroxypropyl-beta-cyclodextrin as a vehicle in order to administer MS-PPOH in vivo. One hour after administration, MS-PPOH (5 mg, IV bolus) significantly inhibited arachidonic acid epoxidation in rat renal cortical microsomes (vehicle-282 +/- 12 pmol/mg/min, MS-PPOH-206 +/- 10 pmol/mg/min, p < 0.05) but had no effect on 20-HETE formation (vehicle-383 32 pmol/mg/min, MS-PPOH-367 +/- 9 pmol/mg/min). The inhibitory effect lasts at least for 6 hours. There was no inhibition of 20-HETE synthesis at any time point. We also examined the effect of MS-PPOH on renal excretiry function. Three hours after MS-PPOH administration to anesthetized rats, urine flow rate became significantly higher (vehicle-275 +/- 16 microl/hour, MS-PPOH-406 +/- 44 microl/hour, p < 0.05). Sodium excretion rate was also significantly higher (vehicle-28.7 +/- 4 micromol/hour, MS-PPOH-63.3 +/- 10 micromol/hour, p < 0.05) but potassium excretion rate was not affected (vehicle-65.5 +/- 5 micromol/hour, MS-PPOH-79.2 +/- 2 micromol/hour). These results suggest that MS-PPOH may be useful as a selective inhibitor of CYP-catalyzed arachidonic acid epoxidation in vivo, and implicate EETs and anti-diuretic and anti-natriuretic in the regulation of renal function.

8,11,14-Eicosatrienoic Acid↗
PubMed2000

Juggling hats.

Explore the source record for details and available documents.

Dentist-Patient Relations↗
PubMed1999

Children with cystic fibrosis benefit from massage therapy.

OBJECTIVE: To measure the effects of parents giving massage therapy to their children with cystic fibrosis to reduce anxiety in parents and their children and to improve the children's mood and peak air flow readings. METHODS: Twenty children (5-12 years old) with cystic fibrosis and their parents were randomly assigned to a massage therapy or a reading control group. Parents in the treatment group were instructed and asked to conduct a 20-minute child massage every night at bedtime for one month. Parents in the reading control group were instructed to read for 20 minutes a night with their child for one month. On days 1 and 30, parents and children answered questions relating to present anxiety levels and children answered questions relating to mood, and their peak air flow was measured. RESULTS: Following the first and last massage session, children and parents reported reduced anxiety. Mood and peak air flow readings also improved for children in the massage therapy group. CONCLUSIONS: These findings suggest that parents may reduce anxiety levels by massaging their children with cystic fibrosis and their children may benefit from receiving massage by having less anxiety and improved mood, which in turn may facilitate breathing.

Analysis of Variance↗
PubMed1988

Novel renal arachidonate metabolites.

Cells of the thick ascending limb of the loop of Henle (TALH) metabolize arachidonic acid (AA) via the cytochrome P450 monooxygenase system to biologically active products that are resolved into two peaks, P1 and P2, on reverse-phase HPLC. Each peak contains materials that have characteristic biological activity. P1 contains a material that relaxes blood vessels and is structurally similar to a vasodilator, the 5,6 epoxyeicosatrienoic acid (EET). P2 contains a material that inhibits cardiac Na+-K+-ATPase, the major component of which has been identified as the 11,12 dihydroxyeicosatrienoic acid. In mTALH cells obtained from rabbits made hypertensive by aortic coarctation, there was a selective increase in P1 and P2 formation compared to other renomedullary cells. We have identified AA metabolites in bovine corneal epithelium with biological properties and chemical features similar to those of mTALH cells. 12(R)hydroxyeicosatetraenoic acid (12(R) HETE) a possible derivative of the 11,12-EET, is produced by the cornea and also has been shown to inhibit Na+-K+-ATPase activity. Renal microsomes obtained from spontaneously hypertensive rats (SHRs) also metabolize AA via a cytochrome P450 monooxygenase pathway to three principal biologically active metabolites that are formed in increased amounts during the developmental phase of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

8,11,14-Eicosatrienoic Acid↗
PubMed1988

Renal cytochrome P-450-related arachidonate metabolism in rabbit aortic coarctation.

Cells of the medullary segment of the thick ascending limb of Henle's loop (TALH) convert arachidonic acid (AA) via the cytochrome P-450 monooxygenase pathway to biologically active metabolites: P1, a vasorelaxant, and P2, an inhibitor of Na+-K+-ATPase activity. These AA metabolites may contribute to the renal vascular and metabolic adjustments in response to renal hypoperfusion and the attendant elevation of blood pressure produced by suprarenal aortic coarctation. On the eighth postoperative day, the blood pressures of hypertensive and sham-operated control rabbits were 105 (90-115) and 63 (60-64) mmHg (medians with semiquartile values), respectively (P less than 0.01). Formation of P1 and P2 was increased twofold in TALH cells obtained from hypertensive rabbits: 2.35 (1.79-4.83) and 1.28 (1.56-4.56) micrograms AA converted.mg protein-1.30 min-1 compared with sham-operated rabbits: 1.27 (1.03-1.53) and 0.64 (0.58-1.10) micrograms AA converted.mg protein-1.30 min-1 (P less than 0.05). The profile of biological activity of AA metabolites contained within P1 and P2 was unaffected by aortic coarctation. The cytochrome P-450 monooxygenase-derived AA metabolites may exert a defensive function to limit the degree of TALH cell injury in response to renal hypoperfusion and associated zonal anoxia by reducing energy-dependent Na+-K+-ATPase activity and affecting local vasodilatation.

Animals↗
PubMed1987

Vasoactivity of arachidonic acid epoxides.

Arachidonic acid (AA) can be metabolized to epoxides and their corresponding diols via the cytochrome P450 epoxygenase pathway. We have compared the vascular activity of four synthetically prepared epoxyeicosatrienoic acids, i.e. 5,6-, 8,9-, 11,12- and 14,15-EET (2-20 microM) on the isolated perfused rat tail artery. The 5,6-EET was equipotent with acetylcholine in dose dependently reducing vascular resistance (ED50 = 3.4 +/- 0.5 microM). The 8,9-, 11,12- and 14,15-EETs of AA did not affect vascular resistance; neither did the 5,6-DHET and delta-lactone, hydrolysis products of 5,6-epoxide. We suggest that the 5,6-epoxide, in contrast to other cytochrome P450-derived products, contributes to the regulation of regional vascular tone.

8,11,14-Eicosatrienoic Acid↗
PubMed1987

Y-derived sequences detected in a 45,X male by in situ hybridization.

A two-month-old boy with normal genitalia and descended testes was referred for a suspected hematological disorder. Cytogenetic analysis showed a 45,X chromosome constitution. In situ hybridization with the Y-derived probe 50f (provided by Professor Marc Fellous) was performed utilizing metaphase chromosomes to determine whether Y material could be detected. A significant amount of label (17 of 150 cells) was found on chromosome 5p suggesting a 5;Y translocation. This translocation was verified by high-resolution G-banded and G-11-stained chromosomes.

Child, Preschool↗
PubMed1987

Spontaneous relapse of naproxen-related nephrotic syndrome.

A number of nonsteroidal anti-inflammatory drugs cause nephrotoxicity characterized by nephrotic syndrome, usually with acute renal insufficiency. Remission of proteinuria and renal insufficiency after discontinuation of nonsteroidal anti-inflammatory drug therapy is characteristic. Relapse of nephrotic syndrome in the absence of nonsteroidal anti-inflammatory drug rechallenge has not previously been reported. Nephrotic syndrome developed in an 80-year-old woman taking naproxen, and remitted after discontinuation of the drug. Nephrotic syndrome relapsed four months later without re-exposure to naproxen or other nonsteroidal anti-inflammatory drugs. Renal biopsy at that time revealed minimal-change disease. The relationship between these two episodes of nephrotic syndrome is discussed with regard to possible pathogenetic mechanisms.

Aged↗
PubMed1986

Cytochrome P450-dependent arachidonate metabolism in renomedullary cells: formation of Na+K+-ATPase inhibitor.

The medullary portion of the thick ascending limb of the loop of Henle (mTALH) has one of the highest concentrations of Na+K+-ATPase found in mammalian tissues, reflecting the importance of this nephron segment in the regulation of extracellular fluid volume, as active sodium transport is driven by Na+K+-ATPase. We have isolated cells derived primarily from the mTALH of the outer medulla of rabbit kidney and have identified a cytochrome P450-dependent mono-oxygenase system which metabolizes arachidonic acid to two biologically active oxygenated peaks, each containing two or more products. One of the peaks potently inhibits cardiac Na+K+-ATPase and the other relaxes blood vessels. We report that formation of these oxygenated arachidonate metabolites is stimulated by arginine vasopressin (AVP) and salmon calcitonin (SCT). In mTALH cells obtained from rabbits made hypertensive by aortic constriction there was a selective increase in P1 and P2 formation compared to other renomedullary cells.

Animals↗
PubMed1985

Enriched prostaglandin E-9 ketoreductase activity in outer medullary cells of the rabbit kidney.

PGE2 metabolism was examined in rabbit renal slices and cell suspensions from the outer medulla, enriched (TALH) and depleted (OMC) for the thick ascending limb of Henle's loop. Metabolism was negligible in intact cells, either OMC or TALH fractions. However, in OMC and TALH homogenates, transformation of PGE2 to PGF2 alpha by NADPH-dependent prostaglandin E-9 ketoreductase (PGE-9KR) was observed at a PGE2 concentration of 4 X 10(-9) M. This activity was not reversible and was enriched ten-fold in the TALH with 41% of PGE2 transformed to PGF2 alpha after 30 min incubation. PGF2 alpha formation from PGE2 could not be detected in homogenates of cortex, medulla or papilla. PGE-9KR activity, particularly in the thick ascending limb, may be a source of PGF2 alpha in urine.

Animals↗
PubMed1984

Conversion of arachidonic acid to two novel products by a cytochrome P450-dependent mixed-function oxidase in polymorphonuclear leukocytes.

Canine polymorphonuclear leukocytes metabolize [14C] arachidonic acid into 2 unidentified products, separated by thin-layer chromatography and high performance liquid chromatography, and called peak 1 and peak 2. The formation of peak 1 is maximal at 5 minutes and then declines, while the synthesis of peak 2 increases throughout the 30 minute incubation period. The formation of peak 1 and, to a lesser extent, peak 2, was enhanced after dual inhibition of lipoxygenase and cyclo-oxygenase enzymes with BW755C (94 microns) or nafazatrom (37 microns), or after incubation in a calcium-free buffer. In contrast, the formation of these products was inhibited by SKF-525A (50 microns), suggesting a cytochrome P450-dependent mechanism. The presence of cytochrome P450 in neutrophil microsomes was confirmed by measuring aryl hydrocarbon hydroxylase activity and cytochrome P450 content.

Animals↗
PubMed1984

Regulation of major histocompatibility gene expression in teratocarcinoma 402AX cells.

Teratocarcinoma 402AX cells are induced to express major histocompatibility complex (MHC) antigens when passaged in vivo in genetically resistant host mice. Studies reported here demonstrate that MHC antigen induction is regulated in vivo in part by the synergistic action of Lyt 1 and Lyt 2 positive splenic T cells and in vitro by serum from tumor-primed resistant mice. Northern blots suggest that some teratocarcinoma 402AX MHC class I antigens may be post-transcriptionally regulated.

Animals↗