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J McCormick

Publications and source records attributed to J McCormick.

At least 55 records · Page 3Linked to original sources
PubMed1995

Cellular expression of the Drosophila melanogaster FMRFamide neuropeptide gene product DPKQDFMRFamide. Evidence for differential processing of the FMRFamide polypeptide precursor.

DPKQDFMRFamide is one of five different FMRFamide-containing peptides encoded in the Drosophila FMRFamide gene. To study the cellular expression of DPKQDFMRFamide, we have generated antisera to DPKQD, the N-terminal sequence of the peptide, to avoid crossreactivity with other -FMRFamide-containing peptides. The antisera were purified and the specificity characterized. DPKQDFMRFamide immunoreactive material is first observed in the embryonic central nervous system (CNS) in one cell of the subesophageal ganglion and one cell in each of the three thoracic ganglia. This pattern of expression is observed in larval, pupal, and adult neural tissue, albeit with increased signal intensity. In larva, pupa, and adult, additional cells in the superior protocerebrum, a thoracic ganglion, and an abdominal ganglion express DPKQDFMRFamide immunoreactive material. Immunoreactivity is observed in a cell in the lateral protocerebrum of pupa and adult and cells in the optic lobe of adult. No immunoreactive material was observed in gut tissue. DPKQDFMRFamide antisera stain a subset of cells previously identified by in situ hybridization and immunocytochemistry to express the FMRFamide transcript and polypeptide precursor. These data suggest that the Drosophila FMRFamide polypeptide precursor undergoes differential processing to produce DPKQDFMRFamide immunoreactive material in a limited number of cells expressing the FMRFamide precursor.

Amino Acid Sequence↗
PubMed1995

Phase I clinical trial of pyrazoloacridine NSC366140 (PD115934).

The pyrazoloacridine (PZA) analogue NSC366140 (PD115934) entered clinical trial based on unique preclinical characteristics including solid tumor selectivity in vitro, marked antitumor activity in vivo against murine solid tumors, selectivity against noncycling cells, and activity against multidrug-resistant tumor cells. After identification of the pre-clinical efficacy and an acceptable toxicity profile, a Phase I study of PZA was carried out. A total of 28 patients was entered and received a total of 67 treatment courses. The drug was administered via a 1-h infusion every 21 days. The starting dose was 30 mg/m2 with 2-fold dose escalations through 480 mg/m2. The next dose escalation was 50%, to 720 mg/m2. Grade I through grade IV toxicities were observed. Since no dose-limiting toxicities were observed at 480 mg/m2, and up to grade IV toxicities were observed at 720 mg/m2, an intermediate dose, 600 mg/m2, was evaluated. Dose-limiting toxicities at 720 mg/m2 were hematological (grade III and IV neutropenia) in four of six patients and neurological (up to grade III cerebral toxicities, including restlessness, dizziness, agitation/anxiety, personality changes, and nightmares, as well as myoclonus) in three of six patients treated. The pharmacokinetic parameters which helped predict these toxicities included area under the curve and peak plasma level. Pharmacokinetic studies showed interpatient variations in all parameters studied. The mean area under the curve levels of PZA at the highest two dose levels in patients were near the level detected in mice at their maximum tolerated total dose. The recommended starting dose for Phase II trials using this schedule is 600 mg/m2.

Acridines↗
PubMed1994

Purification, characterization, gene sequence, and significance of a bacterioferritin from Mycobacterium leprae.

The study of tissue-derived Mycobacterium leprae provides insights to the immunopathology of leprosy and helps identify broad molecular features necessary for mycobacterial parasitism. A major membrane protein (MMP-II) of in vivo-derived M. leprae previously recognized (Hunter, S.W., B. Rivoire, V. Mehra, B.R. Bloom, and P.J. Brennan. 1990. J. Biol. Chem. 265:14065) was purified from extracts of the organism and partial amino acid sequence obtained. This information allowed recognition, within one of the cosmids that encompass the entire M. leprae genome, of a complete gene, bfr, encoding a protein of subunit size 18.2 kD. The amino acid sequence deduced from the major membrane protein II (MMP-II) gene revealed considerable homology to several bacterioferritins. Analysis of the native protein demonstrated the iron content, absorption spectrum, and large native molecular mass (380 kD) of several known bacterioferritins. The ferroxidase-center residues typical of ferritins were conserved in the M. leprae product. Oligonucleotides derived from the amino acid sequence of M. leprae bacterioferritin enabled amplification of much of the MMP-II gene and the detection of homologous sequences in Mycobacterium paratuberculosis, Mycobacterium avium, Mycobacterium tuberculosis, Mycobacterium intracellulare, and Mycobacterium scrofulaceum. The role of this iron-rich protein in the virulence of M. leprae is discussed.

Amino Acid Sequence↗
PubMed1994

Interaction among ET-1, endothelium-derived nitric oxide, and prostacyclin in pulmonary arteries and veins.

Endothelin-1 causes vasodilation of the intact porcine pulmonary vascular bed. To determine the cause of this vasodilation, we investigated the interactions of endothelin-1 (ET-1), endothelium-derived nitric oxide (EDNO), and prostacyclin in isolated small porcine pulmonary arteries and veins under in vitro conditions. ET-1 caused concentration-dependent contractions in arteries and veins, augmented by the nitric oxide synthase (NOS) inhibitor, N omega-nitro-L-arginine, in pulmonary veins. BQ-123 (ETA-receptor antagonist) depressed the ET-1-induced contractions. Sarafotoxin S6C, an ETB-receptor agonist, caused contractions of pulmonary veins only. Endothelium-dependent relaxations to bradykinin and ET-1 were greater in pulmonary veins compared with arteries, inhibited by N omega-nitro-L-arginine, and reversed by L-arginine. BQ-123 augmented ET-1-induced arterial relaxation. ET-3 and sarafotoxin S6C, ETB-receptor agonists, caused comparable endothelium-dependent relaxations in arteries and veins. ET-1 caused a fourfold greater increase in prostacyclin release in pulmonary veins compared with arteries. We conclude that ET-1 is a potent vasoconstrictor of porcine pulmonary vessels and stimulates the release of EDNO and prostacyclin, which oppose the contractions to the peptide. The release of these endothelium-derived vasodilators appears greater in pulmonary veins.

Animals↗
PubMed1994

Characterization of sodium-dependent glucose transport in sheep tracheal epithelium.

The nonmetabolizable glucose analogue methyl(alpha-D-[U-14C]gluco)pyranoside ([14C]AMG) was used to study sodium-dependent glucose transport in two preparations: 1) discs punched from strips of sheep tracheal epithelium, and 2) freshly enzyme-isolated sheep tracheal epithelial cells. In discs, cellular accumulation of [14C]AMG was saturable and exhibited a Michaelis-Menten constant (Km) for AMG of 0.63 +/- 0.15 mM. Uptake was linear over 30 min and was inhibited maximally by 100 microM phlorizin [inhibition constant (Ki) approximately 20 nM], by replacement of external sodium with choline or by addition of 10 mM D-glucose (Ki = 0.19 +/- 0.02 mM). Accumulative uptake was activated, in a concentration-dependent manner, by external sodium [affinity constant (Ka) approximately 23 mM] with a Hill coefficient of greater than one but was abolished on depolarizing with high external potassium. In the presence of sodium, D-galactose and AMG both inhibited uptake of [14C]AMG, whereas L-glucose, D-fructose, and D-mannose were ineffective. In isolated cells, [14C]AMG accumulated only in the presence of external sodium and uptake was inhibited by the addition of D-glucose (Ki approximately 0.2 mM), D-galactose, and AMG but not by L-glucose or D-xylose. We conclude that sheep tracheal epithelium exhibits sodium-dependent glucose uptake with a very high affinity for phlorizin, which indicates the presence of a novel isoform of the transporter.

Animals↗
PubMed1994

Hemodynamics of subarachnoid hemorrhage arrest.

Subarachnoid hemorrhage (SAH) causes a spectrum of clinical syndromes from mild discomfort to rapid brain death. The reason for these heterogeneous consequences is poorly understood. A canine autologous shunt model of SAH was used to study this problem. The duration and volume of hemorrhage into the suprasellar cistern at each animal's mean arterial blood pressure were measured at variable hemorrhage flow rates. At high rates of bleeding in seven dogs (18.7 +/- 2.2 ml/min, mean +/- standard deviation), hemorrhage duration was significantly less (191 +/- 116 seconds, p < 0.03) and hemorrhage volume was significantly greater (15.1 +/- 7.0 ml, p < 0.05) than at low flow rates. At low flow rates of bleeding in nine dogs (4.4 +/- 2.2 ml/min), hemorrhage duration was 394 +/- 202 seconds and volume was 10.9 +/- 6.5 ml. Cerebral perfusion pressure (CPP) decreased at all hemorrhage rates but never to 0 mm Hg (perfusion arrest). No correlation between a decrease in CPP and SAH volume or duration was identified. The initial flow rate of SAH had a positive linear correlation with the volume of hemorrhage (23 dogs, r = 0.64, p < 0.01). The data suggest that initial SAH flow rate, and not CPP, has a primary influence on hemorrhage arrest. This finding may influence the clinical rationale for acute management of SAH-induced brain injury.

Animals↗
PubMed1993

Spatial and temporal expression identify dromyosuppressin as a brain-gut peptide in Drosophila melanogaster.

The Drosophila dromyosuppressin peptide (TDVDHVFLRFamide) is a member of a family of peptides containing the common C-terminal sequence-RFamide. Dromyosuppressin shares a high degree of sequence homology with leucomyosuppressin isolated from cockroach (pEDVDHVFLRFamide) and identity with neomyosuppressin isolated from fleshfly. By means of sequence-specific antisera, the cellular expression pattern of dromyosuppressin immunoreactive material was determined for all stages of Drosophila development. Dromyosuppressin immunoreactivity first appears in two cells of the medial protocerebrum in embryos. The larval stage is characterized by an increase in the number of dromyosuppressin immunoreactive cells in the brain and the first appearance of cellular expression in the ventral ganglion. Immunoreactive fibers extend from the medial protocerebrum cells into the ventral ganglion. Relative to the larval stage, the pupal and adult stages are marked by an increase in the number of immunoreactive cells in the central nervous system and an increase in the arborization of immunoreactive fibers extending from these cells. Immunoreactivity is present in larvae in two cells near the anus; in the adult gut, expression is observed in two cells in the rectum and immunoreactive fibers in the crop that appear to extend from the central nervous system. In general, the number of cells containing dromyosuppressin immunoreactive material increases throughout Drosophila development. However, expression in three cells is restricted to specific developmental periods. These data identify dromyosuppressin as a brain-gut peptide regulated at both a cellular and developmental level.

Amino Acid Sequence↗
PubMed1993

Parenteral nutrition associated with increased infection rate in children with cancer.

BACKGROUND: Recent meta-analyses of published controlled studies concluded that adult patients with cancer randomly assigned to receive parenteral nutrition had higher rates of infectious complications than control subjects. METHODS: The infection risk associated with parenteral nutrition was assessed in 310 pediatric patients with cancer. These patients had central venous access devices (CVAD), Hickman/Broviac (H/B) catheters, or implantable subcutaneous ports in place for the delivery of chemotherapy and supportive care. RESULTS: The median duration of CVAD placement was 363 days; a total of 450 patient years (i.e., the sum of the total years of catheters experienced from all patients studied) were examined. Overall, the infection rate was 0.06 infections/100 days. During the period of parenteral nutrition administration, the rate increased to 0.5 infections/100 days. Among patients who received parenteral nutrition, there were no significant differences in any clinical parameter between the patients who developed an infection and those who did not. When evaluating the entire study population, infection was more likely to occur in patients who had acute nonlymphocytic leukemia (P < 0.01) or H/B catheters (P < 0.01), or who received parenteral nutrition (P < 0.02); there was no relationship between infection and catheter duration, days hospitalized, or days neutropenic (absolute neutrophil count < 0.5 x 10(9)/l). Only CVAD type and parenteral nutrition retained significance in a multivariate Cox proportional hazards model. After adjustment for diagnosis and CVAD type, the risk of infection was 2.4-fold greater in patients given parenteral nutrition (95% confidence interval 1.5 to 3.9; P < 0.001). CONCLUSION: These data confirm that administration of parenteral nutrition is associated with an increased risk of infection in children who have CVAD in place for cancer therapy.

Adolescent↗
PubMed1993

In praise of stinks.

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Air Pollution, Indoor↗
PubMed1993

James Mackenzie.

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Coronary Disease↗
PubMed1993

Antinociceptive actions of BW373U86 in the mouse.

This study explored the antinociceptive properties of (+-)-4-[(alpha- R*)-alpha-[(2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinol]-3-hydroxy benzyl] - N,N-diethyl-benzamide dihydrochloride (BW373U86) a nonpeptidic compound proposed to be a delta opioid agonist, using three models of nociception and four routes of administration in mice. BW373U86 produced dose- and time-dependent, naloxone-sensitive antinociception in both the tail-flick and tail-pinch assays when given intrathecally (i.t.). However, at doses up to 187 nmol/mouse, i.c.v. BW373U86 was inactive in the tail-flick or tail-pinch assays. Additionally, at doses up to 187 mumol/kg, BW373U86 was not active after i.p. or p.o. administration in these endpoints. Further, in the tail-flick test, i.c.v. BW373U86 did not antagonize the antinociceptive effects of i.c.v. [D-Pen2,D-Pen5]enkephalin or [D-Ala2,Glu4]deltorphin, but partially antagonized the effects of i.c.v. morphine. In the acetic-acid abdominal constriction assay, BW373U86 produced dose-dependent antinociceptive effects when given by the i.p., i.c.v. or i.t., but not by the p.o., routes. Intrathecal BW373U86 was 663-fold more potent in the abdominal constriction assay than when given by the same route in the tail-flick test. The effects of an A70 dose of i.p. or i.c.v. BW373U86 in the abdominal constriction assay were partially antagonized by i.c.v. naloxone, but not by i.c.v. N,N-diallyl-Tyr-Aib- Aib-Phe-Leu-OH, where Aib is alpha-aminoisobutyric acid (ICI-174,864) or naltrindole. In contrast, i.t. naloxone, ICI-174,864 or naltrindole antagonized the antinociceptive effect of i.p. or i.t. BW373U86 in the abdominal constriction assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1992

Maasai diet.

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Diet Surveys↗
PubMed1991

Doctors and AIDS.

Just a year ago most authorities considered the chances of patients contracting AIDS from doctors and other healthcare workers a virtual impossibility. But last week a Florida woman who got AIDS from her dentist lay near death, and two Minneapolis physicians admitted they had treated hundreds of patients since being diagnosed with the virus. Although doctors are at far greater risk than patients, the Minneapolis cases renewed the debate over the right of sides to know each other's HIV status.

Acquired Immunodeficiency Syndrome↗