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Biomedical subjects

D Schwartz

Publications and source records attributed to D Schwartz.

At least 73 records · Page 4Linked to original sources
PubMed2000

Bioactive products of arginine in sepsis: tissue and plasma composition after LPS and iNOS blockade.

Blockade or gene deletion of inducible nitric oxide synthase (iNOS) fails to fully abrogate all the sequelae leading to the high morbidity of septicemia. An increase in substrate uptake may be necessary for the increased production of nitric oxide (NO), but arginine is also a precursor for other bioactive products. Herein, we demonstrate an increase in alternate arginine products via arginine and ornithine decarboxylase in rats given lipopolysaccharide (LPS). The expression of iNOS mRNA in renal tissue was evident 60 but not 30 min post-LPS, yet a rapid decrease in blood pressure was obtained within 30 min that was completely inhibited by selective iNOS blockade. Plasma levels of arginine and ornithine decreased by at least 30% within 60 min of LPS administration, an effect not inhibited by the iNOS blocker L-N(6)(1-iminoethyl)lysine (L-NIL). Significant increases in plasma nitrates and citrulline occurred only 3-4 h post-LPS, an effect blocked by L-NIL pretreatment. The intracellular composition of organs harvested 6 h post-LPS reflected tissue-specific profiles of arginine and related metabolites. Tissue arginine concentration, normally an order of magnitude higher than in plasma, did not decrease after LPS. Pretreatment with L-NIL had a significant impact on the disposition of tissue arginine that was organ specific. These data demonstrate changes in arginine metabolism before and after de novo iNOS activity. Selective blockade of iNOS did not prevent uptake and can deregulate the production of other bioactive arginine metabolites.

Animals↗
PubMed2000

Glomerular basement membrane anionic sites in adriamycin nephropathy: effect of saline loading and nitric oxide modulation.

BACKGROUND: In previous studies we found that experimental Adriamycin (ADR) nephropathy is associated with the loss of glomerular basement membrane (GBM) anionic sites provided by heparan sulfate proteoglycans. Chronic saline loading in normal rats resulted in a similar effect on the GBM anionic sites. The L-arginine-nitric oxide synthase-nitric oxide system is involved in the pathogenesis of experimental chronic renal failure. The present study was performed to determine the combined effect of nitric oxide (NO) modulation and chronic saline loading in ADR nephropathy. The modulation of NO was done by chronic administration of L-arginine (NO donor) or N(w)-nitro-L-arginine, a known nitric oxide synthase inhibitor. METHODS: Systolic blood pressure was measured in awake rats by a tail-cuff method. Renal function was assessed by creatinine clearance, FeNa%, and daily protein excretion. The change of mean GBM widths and anionic sites distribution were assessed by electron microscopy. The localization of anionic sites was carried out by cationic colloidal gold. Plasma and urinary nitrates (NO(x)) were measured by nitrite (NO(2)) + nitrate (NO(3)), stable metabolites of NO. RESULTS: Two weeks after the ADR administration (3.5 mg/kg BW iv) the rats had severe renal failure (creatinine clearance 134 +/- 31 microl/min/100 g BW vs. initial values 670 +/- 29 microl/min/ 100 g BW, p < 0.001), high FeNa%, severe proteinuria, increased GBM width, significant reduction of GBM anionic sites and low urinary NO(x) excretion. The saline loading resulted in further reduction of GBM anionic sites count and blood pressure elevation. The inhibition of NO did not change the course of ADR nephropathy. The main finding of the present study is that chronic administration of L-arginine significantly alleviates the renal failure in the ADR (+/- saline loading) nephropathy. The L-arginine-treated rat had higher creatinine clearance, lower FeNa% and protein excretion and complete normalization of GBM anionic sites distribution. CONCLUSIONS: Sodium loading has a deleterious effect on GBM permselectivity. L-Arginine prevents the reduction of GBM anionic sites, decreases proteinuria and alleviates the renal insufficiency in ADR nephropathy.

Animals↗
PubMed2000

Biopsy-based comparison of liquid-based, thin-layer preparations to conventional Pap smears.

OBJECTIVE: To evaluate and compare histologic diagnosis of squamous intraepithelial neoplasia and cancer of the cervix with cytologic diagnosis using the conventional Pap smear versus the AutoCyte PREP liquid-based, thin-layer preparation. STUDY DESIGN: Two randomly selected, large patient groups from the same population were studied using two different cervical cytology preparation techniques. Cytologic results were compared to histologic diagnosis to estimate the relative sensitivities and specificities of the preparations. RESULTS: AutoCyte's liquid-based, thin-layer preparation method demonstrated improved agreement with histologic diagnosis as compared to the conventional Pap smear. This result supported the previously reported finding that use of this thin-layer method reduced atypical squamous cells of undetermined significance cases and substantially increased the detection of squamous intraepithelial lesions (SILs). CONCLUSION: Our cytohistologic correlation for conventional Pap smears and the AutoCyte PREP liquid-based preparations demonstrate that the increased rate of both low and high grade SILs on AutoCyte PREP reflects real detection as opposed to overdiagnosis.

Biopsy↗
PubMed2000

Community violence exposure and children's social adjustment in the school peer group: the mediating roles of emotion regulation and social cognition.

This study reports a cross-sectional investigation of the relation between community violence exposure and peer group social maladjustment in 285 inner-city children in Grades 4-6 (mean age = 10.3 years). Children completed an inventory assessing exposure to community violence through witnessing and through direct victimization. A peer nomination inventory was then administered to assess social adjustment with peers (aggression, peer rejection, and bullying by peers). In addition, social-cognitive biases and emotion regulation capacities were examined as potential mediators. Analyses indicated that violent victimization was associated with negative social outcomes through the mediation of emotion dysregulation. Witnessed violence was linked only to aggressive behavior. Social information processing, rather than emotion dysregulation, appeared to mediate this association. These results demonstrate that violence exposure is linked to multiple levels of behavioral and social maladjustment and suggest that there are distinct patterns of risk associated with different forms of exposure.

Aggression↗
PubMed2000

Follow-up care for cancer: making the benefits equal the cost.

Posttreatment follow-up is a staple of oncologic practice. Clinicians have traditionally presumed that close surveillance improves clinical outcome. However, new evidence reveals that frequent, procedure-intensive follow-up may provide no more significant benefit to patients than simpler approaches. Several recent consensus recommendations from major oncology organizations support this theory. Published surveys of clinician and institutional follow-up policies reveal significant variations in practice, with many providers continuing to use costly, unproven regimens. This review highlights current data on follow-up care for three common cancers--breast, colorectal, and prostate. These data suggest an acute need for changes leading to more rational, consistent, and efficient follow-up practices.

Aftercare↗
PubMed2000

[Functional imaging of the auditory cortex: role of magnetoencephalography].

We present the different methods for detecting cerebral activity in the auditory cortex. Positron emission tomography (PET) and functional MRI (fMRI) measure such activity indirectly by calculating the blood flow rate or the consumption of oxygen. The direct methods of detection record the electrical or magnetic activity by eletroencephalography (EEG), or magnetoencephalography (MEG), respectively. The aim of this study was to define the role of MEG amongst these different techniques using the data from recordings of evoked magnetic fields in 5 healthy subjects. The localizations demonstrated the tonotopic organization of the auditory cortex, with high-pitched sounds showing a more medial cortical projection than low-pitched sounds. These various techniques are complementary. PET allows a pharmacological study of the cortex, and could be used in patients with cochlear implants. FMRI is non-invasive, and has a high spatial resolution. EEG has an excellent temporal resolution, and EEG recordings do not require major equipment or infrastructure. MEG has a better spatial resolution, with the same temporal resolution, as EEC. MEG is particularly useful in the localization of the cortical generators of middle-latency auditory evoked responses.

Adult↗
PubMed1999

Epithelial cells of different organs exhibit distinct patterns of p53-dependent and p53-independent apoptosis following DNA insult.

The present study shows that DNA damage induces different patterns of p53-dependent and p53-independent apoptosis in epithelial cells of various organs of adult mice. Genotoxic stress induced a biphasic apoptotic response in the small intestine and tongue. While the first immediate apoptotic wave was p53-dependent, the second was slower in rate and was p53-independent. Under the same experimental conditions a single rapid, but a more extended, p53-independent response was evident in the skin of the tail. Indeed, exposure of p53+/+ mice to 400 R induced in epithelium of the small intestine and tongue an immediate rapid response that was followed by a second delayed p53-independent apoptotic wave. p53-/- mice exhibited in these organs the second wave only. However, epithelium of the tail derived from the same mice showed a single rapid apoptotic response that lasted much longer than the p53-dependent response and was similar in the p53-/- and the p53+/+ mice. Variations in apoptotic patterns observed in epithelial cells derived of the different tissues may point to differences in the physiological pathways expressed.

Animals↗
PubMed1999

Accentuated apoptosis in normally developing p53 knockout mouse embryos following genotoxic stress.

In order to identify the alternative pathways which may substitute for the p53 function during embryogenesis, we have focused our studies on p53 -/- normally developing mouse embryos that survived a genotoxic stress. We assumed that under these conditions p53-independent pathways, which physiologically control genomic stability, are enhanced. We found that while p53 +/+ mouse embryos elicited, as expected, a p53-dependent apoptosis, p53-/- normally developing mice exhibited an accentuated p53-independent apoptotic response. The p53-dependent apoptosis detected in p53+/+ embryos, was an immediate reaction mostly detected in the brain, whereas the p53-independent apoptosis was a delayed reaction with a prominent pattern observed in epithelial cells of most organs in the p53-deficient mice only. These results suggest that in the absence of p53-dependent apoptosis, which is a fast response to damaged DNA, p53-independent apoptotic pathways, with slower kinetics, are turned on to secure genome stability.

Animals↗
PubMed1999

Time course of lipopolysaccharide-induced nitric oxide synthase mRNA expression in rat glomeruli.

The decrease in glomerular filtration rate that is characteristic of sepsis has been shown to result from the local glomerular inhibition of endothelial nitric oxide synthase (NOS) by nitric oxide (NO) generated from the inducible isoform of NOS (iNOS). iNOS activation depends on de novo synthesis of both RNA and protein. Therefore it is assumed that several hours are required for its full activation. Yet the renal hemodynamic response in sepsis has been documented as early as 60 minutes after lipopolysaccharide (LPS) administration. Experiments were designed to determine the time course of LPS-induced glomerular iNOS mRNA expression and activity in rats. Rats were treated with LPS (2 mg/kg body weight IP). Kidneys were removed after 1,2, 4, 6, and 16 hours. Glomeruli were isolated and incubated. Nitric oxide generation was measured with a Griess assay, and iNOS mRNA was studied by reverse transcriptase-polymerase chain reaction. Similar time course experiments were repeated in glomeruli isolated from normal rats and exposed to LPS in vitro. A significant increase in iNOS mRNA expression was evident as early as 60 minutes after both in vivo and in vitro administration of LPS. The quantity of iNOS mRNA reached its peak between 2 to 4 hours after administration and declined to baseline levels after 16 hours. Immunohistochemical studies were remarkable for a significant increase in the staining for iNOS in glomeruli 2 hours after the in vivo administration of LPS. Plasma nitric oxide concentration after the in vivo administration of LPS increased from a baseline level of 11.25 +/- 0.8 micromol/L to a peak level of 62.9 +/- 3.8 micromol/L (P < .05 vs baseline) at 4 hours and then decreased to 17.5 +/-1.9 micromol/L at 16 hours. Similar results were obtained when the glomerular generation of nitric oxide after in vivo administration of LPS was measured (2.6 +/- 0.8 pmol/h/microg tissue, 17.2 +/- 2.1 pmol/h/microg tissue (P < .05 vs baseline), and 0.4 +/- 0.65 pmol/h/microg tissue, respectively). These results provide evidence of the rapid activation of glomerular iNOS after in vivo and ex vivo administration of LPS and thus support the role of nitric oxide in the early renal hemodynamic response to LPS.

Animals↗
PubMed1999

Simian virus 40-transformed metallothionein null cells showed increased sensitivity to cadmium but not to zinc, copper, mercury or nickel.

Primary cultured embryonic cells derived from mice with disrupted metallothionein (MT) I and II genes and from control mice were transformed with a plasmid encoding the simian virus 40 (SV40) large T antigen. The resulting MT-/- and MT+/+ cell strains showed similar cell morphology, cell cycle and no significant differences in glutathione levels or in the activities of glutathione-related enzymes and antioxidant enzymes. The MT-/- cells were more sensitive to Cd than MT+/+ cells, though no increase in the sensitivity to Zn, Cu, Hg or Ni were observed in MT-/- cells. MT+/+ cells accumulated more Cd than MT-/- cells but showed less lesion, suggesting the role of MT induced by Cd in MT+/+ cells as a scavenger of toxic Cd ion. These results suggest a dominant protective role of MT against Cd compared with other metals. SV40-transformed MT-/- cells seem to be a useful tool for the investigation of cellular function of MT.

Animals↗
PubMed1999

Early behavior problems as a predictor of later peer group victimization: moderators and mediators in the pathways of social risk.

This study is a prospective investigation of the predictive association between early behavior problems (internalizing, externalizing, hyperactivity-impulsiveness, immaturity-dependency) and later victimization in the peer group. Teacher ratings of the behavioral adjustment of 389 kindergarten and 1st-grade children (approximate age range of 5 to 6 years-old) were obtained, using standardized behavior problem checklists. These ratings predicted peer nomination scores for victimization, obtained 3 years later, even after the prediction associated with concurrent behavior problems was statistically controlled. Further analyses suggested that the relation between early behavior problems and later victimization is mediated by peer rejection and moderated by children's dyadic friendships. Behavior problems appear to play an important role in determining victimization within the peer group, although the relevant pathways are complex and influenced by other aspects of children's social adjustment.

Aggression↗
PubMed1999

It takes two to fight: a test of relational factors and a method for assessing aggressive dyads.

Observations of aggressive interactions in boys' laboratory play groups were used to evaluate the relative importance of relational and individual factors in accounting for aggressive acts. A classroom peer-rating method for identifying mutually aggressive dyads was validated in 11 5-session play groups, composed of 2 mutually aggressive boys and 4 randomly selected male classmates from 11 predominately African American 3rd-grade classrooms. When the social relations model was used, relationship effects accounted for equally as much of the variance in total aggression and proactive aggression as either actor or target effects. Mutually aggressive dyads displayed twice as much total aggression as randomly selected dyads. Members of mutually aggressive dyads attributed greater hostile intentions toward each other than did randomly selected dyads, which may serve to explain their greater aggression toward each other. The importance of studying relational factors, including social histories and social-cognitive processes, is discussed.

Aggression↗
PubMed1999

A comparison of two concentrations of bupivacaine and adrenaline with and without fentanyl in paediatric inguinal herniorrhaphy.

This study was designed to determine whether administration of caudal bupivacaine with fentanyl would have any effect on analgesia in paediatric patients undergoing inguinal herniorrhaphy repair. Fifty-six outpatient paediatric patients undergoing inguinal hernia repair were evaluated. Patients received, in a randomized manner, 1 ml.kg-1 of either bupivacaine 0.25% or 0.125% with or without fentanyl 1 microg.kg-1. There was no difference in pain scores in the hospital, the night of surgery, or 24 h postoperatively nor was there a difference in the oral analgesics administered between any of the groups. There was a higher incidence of vomiting at home in both 0.25% bupivacaine groups irrespective of the use of fentanyl. The 0.125% bupivacaine group had significantly more patients who received intravenous fentanyl in the PACU than did the other three groups (P<0.001). Increasing the concentration of bupivacaine from 0. 125% to 0.25% increased the incidence of postoperative vomiting. We recommend that clinicians utilize bupivacaine 0.125% with 1 microg. kg-1 fentanyl as the caudal injectate in paediatric patients undergoing inguinal hernia repair.

Administration, Oral↗
PubMed1999

Intravenous iron for the treatment of predialysis anemia.

This article, based on our own studies and those of others, presents evidence to show that the anemia of chronic renal failure in the predialysis period is, to a significant extent, caused by iron deficiency and can be improved in most cases by the administration of intravenous (i.v.) but not oral iron. We estimate that in approximately 30% of all predialysis patients with anemia, a target hematocrit (Hct) of 35% can be reached and maintained by giving i.v. iron alone without exceeding currently acceptable limits of serum ferritin (500 microg/liter) or the percentage of iron saturation (40%). If, in addition, subcutaneous erythropoietin (EPO-usually in only low doses-is added, the combination has an additive effect on the Hct response, and almost all anemic predialysis patients can reach and maintain the target Hct of 35% over a one-year period. Therefore, the advantage of maintaining adequate iron stores with i.v. iron is that if EPO is needed, lower doses will be required to achieve the target Hct than if EPO were used alone. This not only avoids the high cost of EPO therapy but also its associated side-effects, especially hypertension. Using Venofer, a ferric hydroxide sucrose complex, as our i.v. iron supplement, we have seen no anaphylactic reactions in over 20,000 infusions over a four-year period in 360 hemodialysis, 123 predialysis, and 58 peritoneal dialysis patients.

Administration, Oral↗
PubMed1999

Inactivation of the tricarboxylic acid cycle aconitase gene from Streptomyces viridochromogenes Tü494 impairs morphological and physiological differentiation.

The tricarboxylic acid (TCA) cycle aconitase gene acnA from Streptomyces viridochromogenes Tü494 was cloned and analyzed. AcnA catalyzes the isomerization of citrate to isocitrate in the TCA cycle, as indicated by the ability of acnA to complement the aconitase-deficient Escherichia coli mutant JRG3259. An acnA mutant was unable to develop aerial mycelium and to sporulate, resulting in a bald phenotype. Furthermore, the mutant did not produce the antibiotic phosphinothricin tripeptide, demonstrating that AcnA also affects physiological differentiation.

Aconitate Hydratase↗
PubMed1999

Temporal adjustment of the juxtaglomerular apparatus during sustained inhibition of proximal reabsorption.

Tubuloglomerular feedback (TGF) stabilizes nephron function by causing changes in single-nephron GFR (SNGFR) to compensate for changes in late proximal flow (VLP). TGF responds within seconds and reacts over a narrow range of VLP that surrounds normal VLP. To accommodate sustained increases in VLP, TGF must reset around the new flow. We studied TGF resetting by inhibiting proximal reabsorption with benzolamide (BNZ; administered repeatedly over a 24-hour period) in Wistar-Froemter rats. BNZ acutely activates TGF, thereby reducing SNGFR. Micropuncture was performed 6-10 hours after the fourth BNZ dose, when diuresis had subsided. BNZ caused glomerular hyperfiltration, which was prevented with inhibitors of macula densa nitric oxide synthase (NOS). Because of hyperfiltration, BNZ increased VLP and distal flow, but did not affect the basal TGF stimulus (early distal salt concentration). BNZ slightly blunted normalized maximum TGF response and the basal state of TGF activation. BNZ sensitized SNGFR to reduction by S-methyl-thiocitrulline (SMTC) and caused the maximum TGF response to be strengthened by SMTC. Sensitization to type I NOS (NOS-I) blockers correlated with increased macula densa NOS-I immunoreactivity. Tubular transport measurements confirmed that BNZ affected TGF within the juxtaglomerular apparatus. During reduced proximal reabsorption, TGF resets to accommodate increased flow and SNGFR through a mechanism involving macula densa NOS.

Absorption↗