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D Salazar

Publications and source records attributed to D Salazar.

18 recordsLinked to original sources
PubMed1995

Pharmacokinetics and pharmacodynamics of the monoamine oxidase B inhibitor mofegiline assessed during a phase I dose tolerance trial.

The safety, pharmacokinetics, and pharmacodynamics of single oral doses of up to 48 mg and daily (for 28 days) doses of up 24 mg mofegiline were investigated in healthy male volunteers. Plasma pharmacokinetics indicated rapid absorption and elimination: time to reach maximum concentration occurred at about 1 hour; half-life ranged from 1 to 3 hours. Maximal plasma concentration and area under the plasma concentration-time curve increased and oral clearance decreased disproportionately with dose. Mofegiline rapidly and markedly inhibited platelet monoamine oxidase B (MAOB) activity, which returned to baseline within 14 days. Urinary excretion of phenylethylamine increased proportionately with doses up to 24 mg. No changes in urinary elimination of catecholamines, blood pressure, heart rate, or ECG were observed. A classic maximum tolerated dose was not achieved in these studies. However, the 48 mg single dose and the 24 mg multiple daily dose far exceeded the dose (1 mg) that was associated with > 90% platelet MAOB inhibition.

Administration, Oral↗
PubMed1994

Expression and characterization of human and chimeric human-Paracoccus denitrificans electron transfer flavoproteins.

Electron transfer flavoprotein (ETF) is a heterodimer that contains a single equivalent of FAD and accepts electrons from nine flavoprotein dehydrogenases in the mitochondrial matrix. Human ETF was expressed in Escherichia coli using the expression vector previously employed to express Paracoccus denitrificans ETF (Bedzyk, L. A., Escudero, K. W., Gill, R. E., Griffin, K. J., and Frerman, F. E. (1993) J. Biol. Chem. 268, 20211-20217). cDNAs encoding the beta and alpha subunits of the human protein were inserted into the vector, mimicking the arrangement of the P. denitrificans genes in which coding sequences are joined by overlapping termination and initiation codons. A human ETF containing 30% P. denitrificans sequence at the amino terminus of the beta subunit was also expressed and purified. This chimeric ETF has 64% sequence identity with the human sequence in the substituted region. Kinetic constants of medium chain and short chain acyl-CoA dehydrogenases for the chimeric ETFs were slightly changed from those of human ETF; but, there are marked differences in the kinetic constants of sarcosine dehydrogenase and electron transfer flavoprotein-ubiquinone oxidoreductase with the two ETFs. Absorption spectra of the three redox states of human, chimeric, and P. denitrificans ETF flavins are identical. However, the flavin circular dichroism spectra of the three ETFs are characteristic for each species. The spectrum of the chimeric ETF has both human and P. denitrificans ETF features. The amplitude of the 436 nm band is identical to that of the of the human ETF flavin, but the amplitude of the 375 nm band is identical to that of the P. denitrificans ETF flavin. Thus, flavin in the chimeric ETF appears to be exposed to dipoles in the protein framework provided by human and bacterial sequences. These spectral data indicate that the flavin is located in the vicinity of the amino-terminal region of the beta subunit. The kinetic data suggest that the amino-terminal region of the beta subunit comprises part of the docking site for some primary dehydrogenases and electron transfer flavoprotein-ubiquinone oxidoreductase.

Amino Acid Sequence↗
PubMed1987

Characterization of natural cytotoxic effector cells isolated from rat liver.

Nonparenchymal liver cells (NPC) from normal untreated female Wistar/Furth rats were tested for natural cytotoxicity in a 4-hour 51Cr release assay against the murine lymphoma YAC-1, the murine mastocytoma P815, and the syngeneic rat mammary carcinoma TMT-081 tumor cell lines. NPC exerted strong cytotoxicity against all three target cells. In contrast, fresh spleen cells displayed cytotoxicity only against YAC-1, although after culture for 24 h at 37 degrees C cytotoxicity was displayed against all three target cells. Fresh spleen cells contained 2-15% large granular lymphocytes (LGL) as assessed by Giemsa staining whereas NPC contained 10-23% LGL and 10-25% Kupffer cells. Centrifugal elutriation produced fractions that were increased in one or the other of the cell types. More cytotoxic activity was observed in the fraction containing more LGL. The cytolytic activity of fresh spleen cells could be eliminated by either in vivo or in vitro treatment with anti-asialo-GM1 antiserum. On the other hand, the cytolytic activity of NPC was resistant to in vivo treatment, but was partially sensitive to in vitro treatment. Furthermore, the activity of cultured spleen cells was also partially sensitive to in vitro treatment. NPC and cultured spleen cells also were more resistant to suppression by prostaglandin E2 and nordihydroguaiaretic acid than fresh spleen cells. We conclude that LGL is mainly responsible for natural cytotoxicity of NPC and that some effector cells in NPC may be highly activated.

Animals↗
PubMed1985

Natural antitumor defense system of the murine liver.

Murine nonparenchymal liver cells from various genetic strains isolated by collagenase digestion and differential sedimentation contain both lymphocytes and macrophages. Nonparenchymal liver cells as well as spleen cells, mononuclear blood cells, and peritoneal exudate cells from C3HeB/FeJ mice were tested for natural cytotoxicity against YAC-1 (sensitive to NK cells) and P815 (resistant to NK cells) tumor cell lines. Resident peritoneal exudate cells exerted no cytotoxicity against either tumor cell, whereas spleen and mononuclear blood cells lysed only YAC-1. In contrast, nonparenchymal liver cells lysed both YAC-1(4 h) and P815 (18 h) tumor cells. Treatment of nonparenchymal liver cells with anti-asialo GM1 and complement abolished the antitumor activity against both tumor cell lines but not the phagocytic activity. Nonadherent nonparenchymal liver cells exerted greater cytotoxicity against YAC-1 tumor cells but little cytotoxicity against P815 tumor cells when compared with unfractionated cells. Adherent nonparenchymal liver cells (macrophages) from untreated mice exerted no antitumor activity against either tumor cell. In contrast, adherent nonparenchymal liver cells from Corynebacerium parvum treated mice were directly cytotoxic to P815 tumor cells. Spleen cells that are normally not cytotoxic to P815 tumor cells (18 h) became cytotoxic when mixed with adherent nonparenchymal liver cells from untreated mice. These results indicate that the tumoricidal effector cell in nonparenchymal liver cells from untreated mice appears to be the NK cell. Apparently, murine liver macrophages from untreated mice do not have tumoricidal activity per se but can "activate" NK cells to kill tumor cells normally resistant to NK cells.

Animals↗
PubMed1984

Multiple tumoricidal effector mechanisms induced by adriamycin.

The antitumor cytotoxic mechanisms of Adriamycin-elicited peritoneal exudate cells were investigated. Peritoneal exudate cells from mice collected 1 day after an i.p. injection of Adriamycin (10 mg/kg) displayed enhanced cytotoxicity against P815 (natural killer-insensitive, macrophage-sensitive) but not YAC-1 (natural killer-sensitive) tumor cell lines. These cells contained a sufficient concentration of the drug to be cytotoxic for P815 tumor cells in 18-hr chromium release assays. Freeze-thaw lysates of these peritoneal exudate cells were found to be as cytotoxic to P815 as their corresponding whole cells. The lytic activity of these lysates was removed by centrifugation at 100,000 X g, indicating the insolubility of the effector moiety. These cells were also shown to produce significant amounts of superoxide anion and H2O2 in response to phorbol myristate acetate. A catalase-inhibitable augmentation of the cytotoxicity of these cells against P815 was observed when phorbol myristate acetate was added to the assay. Neutrophils and not macrophages were likely responsible for this effect. Peritoneal lymphocytes from mice given injections of Adriamycin 5 to 7 days previously were cytotoxic to YAC-1 tumor cells in 4-hr assays. Finally, peritoneal macrophages harvested 5 to 7 days after Adriamycin administration were cytotoxic to P815 in the absence of detectable Adriamycin. The addition of phorbol myristate acetate inhibited the lysis of P815 by these cells.

Animals↗
PubMed1983

Adriamycin-induced activation of NK activity may initially involve LAF production.

C3HeB/FeJ spleen cells (unseparated or passaged over nylon wool columns) were cultured overnight (1-2 X 10(6) cells/microwell) in the presence and absence of resident or ADM-induced PEC and anti-YAC-1 (4h) NK activity was determined. The addition of resident PEC to spleen cells had little effect on NK activity. However, the addition of ADM-elicited PEC (10 mg/kg, IP, day -1 and day -5) to spleen cells prior to culture significantly augmented NK activity. If ADM-induced PEC were treated with carbonyl iron prior to coculture with spleen cells, augmentation of anti-YAC-1 activity was not observed. This suggested that ADM-activated macrophages augmented cultured splenic NK activity. Supernatants from overnight-cultured resident or ADM-induced adherent PEC were then prepared, dialyzed (to remove ADM), and tested for mitogenic activity or cocultured with spleen cells overnight. ADM-induced adherent PEC supernatants stimulated the proliferation of murine thymocytes (both LAF and IL-2 also stimulate) but not cultured CTL (only IL-2 stimulates). ADM-induced adherent PEC supernatants (as well as LAF, IL-2, and IFN) augmented overnight-cultured C3HeB/FeJ splenic NK activity. However, only IL-2 and IFN could augment overnight-cultured athymic BALB/c . nu/nu splenic NK activity. This suggested that ADM-elicited macrophages produce LAF which may act directly on NK cells or, more likely, may induce T cells to produce IL-2, IFN, or both.

Animals↗
PubMed1982

Augmentation of murine natural killer activity after culture.

The augmentation of murine natural killer (NK) cell activity after culture is described. Increased NK cell activity occurred when spleen cells were cultured for 18 or 42 h at high cell density in macro culture plates at 37 degrees C. Similar results were also achieved using the same cell density when micro culture plates were employed. The simple modifications of culture conditions described in this paper should provide an excellent tool to study murine NK activity after culture. Furthermore, the micro culture system has the added advantage of enabling one to test large numbers of samples.

Animals↗
PubMed1982

Natural cytotoxicity of isolated rat liver cells.

Unfractionated liver cells and parenchymal liver cells from untreated male Lewis rats were tested for natural cytotoxicity in a 4-hr 51chromium-release assay against YAC-1. Minimal cytotoxicity was observed. Nonparenchymal liver cells obtained by either differential centrifugation or metrizamide gradient centrifugation exerted strong cytotoxicity against YAC-1 and P815. Resident peritoneal exudate cells and spleen cells displayed cytotoxicity only against YAC-1. Furthermore, the cytotoxicity of these nonparenchymal liver cells was diminished by carbonyl iron treatment. Therefore, on the basis of these and other characteristics, the majority of the effector cells in the liver resemble tumoricidal macrophages. Finally, parenchymal liver cells or their cellfree supernatants were able to inhibit the cytotoxicity of these tumoricidal nonparenchymal liver cells, suggesting that the tumoricidal capacity of the liver was under some regulatory control.

Animals↗
PubMed1981

Evaluation of modified gowning procedures in a neonatal intensive care unit.

The effect of modified gowning techniques in a neonatal intensive care unit was evaluated. During alternate two-month intervals, no gowns were worn over street clothes in patient care areas by staff or visitors. Mortality and infections rates during these "modified" gowning intervals were the same as during the gowning periods. However, the incidence of necrotizing enterocolitis was significantly greater in the modified gowning periods (7/353) than in the gowning periods (1/371). An expansion of this one-year study to include another year showed an even greater effect. The prevalence of bacteria at three anatomic sites (nares, umbilicus, and groin) on days 2, 4, 7, 10, 14, 21, and 28 of hospitalization was comparable between those studied during modified gowning and gowning intervals. Exceptions were the significantly increased prevalence of Staphylococcus epidermidis in the groin (days 21 and 28) during gowning and S aureus in the nares (day 28) during modified gowning periods.

Bacterial Infections↗
PubMed1981

Double trisomy 48,XXX,+ 18 in a newborn.

We report the 6th case of double trisomy X and 18 ie, 48,XXX,+ 18. The infant lacked overlapping fingers, simian creases, and structural heart disease and is alive at 275 days. Two X chromosomes were late replicating. Anomalies of the hands and kidneys involved only the right side in the present case; review of the five previous cases of 48,XXX, +18 also showed that anomalies of kidneys, hands, and ears affected predominantly the right side in three patients.

Chromosome Banding↗
PubMed1980

Human milk.

Explore the source record for details and available documents.

Chemotactic Factors↗
PubMed1980

Herniation of the appendix through the umbilical ring following umbilical artery catheterization.

A case of herniation of the appendix through the umbilical ring following transection of the umbilical cord for arterial catheterization is described. After the appendix was returned into the abdominal cavity and the peritoneal edges closed, the patient had no further difficulty. This rare complication of catheterization can be avoided by careful palpation of the umbilical stump and use of a moist bias tape around the base of the umbilicus prior to transection of the cord.

Appendix↗
PubMed1979

Partial trisomy of chromosome 3 (3q12 leads to qter) owing to 3q/18p translocation. A trisomy 3q syndrome.

In four previously reported patients with partial 3q trisomy, only a small portion of 3q was trisomic (3q21 leads to qter or 3q25 leads to qter). Clinical features in these cases have included the following: low-set ears, mongoloid slant of eyes, hypertelorism, cleft palate, webbed neck, simian creases, short finger, clinodactyly, hypotonia, and low-set hairline. Cytogenetic studies of a premature, 1,680-g female infant with with these clinical features showed this extra material to be part of the long arm of chromosome 3 (3q12 leads qter), which resulted in partial trisomy for this segment, ie, 46,XX,-18, +t (3;18) (q12;p11). Although a larger portion of 3q was involved in this case, the clinical picture was similar to other cases of 3q duplication with or without 3p deletion.

Abnormalities, Multiple↗
PubMed1979

Pharmacokinetics and safety of cefamandole in newborn infants.

Cefamandole, a new parenteral cephalosporin antibiotic, was administered to 23 newborn infants with pustular skin infection due to Staphylococcus aureus for an average duration of 7.5 days. All the patients improved clinically. Elevation of serum glutamic oxaloacetic transaminase and eosinophilia were observed in nine infants each transiently during treatment. There were no abnormalities of renal functions and Coombs' test results remained negative. The levels of cefamandole in serum after either intravenous or intramuscular administration were higher and the mean life was longer than those previously reported in older infants, children, and adults.

Cefamandole↗