The effects of human interferons (IFN-alpha, IFN-beta, IFN-gamma) on the replication of Hantaan virus (HV) in Vero E6 cells were examined. Pretreatment of cells with human IFNs resulted in dose-dependent inhibition of HV plaque formation. Of the 3 human IFNs, IFN-beta inhibited virus replication most effectively. Pretreatment of murine macrophage cells with mouse IFN-beta also resulted in an inhibition of viral growth and then the effect of murine IFN-beta in newborn ICR mice infected with HV was also examined. When newborn mice were inoculated intraperitoneally with HV, their survival rate was approximately 20%. When they were treated with interferon 6 h before infection with virus, their survival rate was 85-90%. When IFN and virus were injected simultaneously into the intraperitoneal cavity, the survival rate of the mice was also higher than that of untreated mice. When the mice were treated with IFN for 2 or 7 consecutive days after infection, their survival rate was 70%. These results suggest that IFN may be effective for both prophylactic and therapeutic purposes in Hantaan virus infection.

Animals↗

PubMed1987

A rare case of simultaneous malignant tumors: osteosarcoma of the mandible and lung cancer.

Explore the source record for details and available documents.

Adenocarcinoma↗

PubMed1987

Ventilatory predictors of pulmonary hypoplasia in congenital diaphragmatic hernia, confirmed by morphologic assessment.

We carried out a prospective study in 66 infants with congenital diaphragmatic hernia within the first 6 hours of life to determine whether outcome is related to the degree of underlying pulmonary hypoplasia, as predicted by preoperative PaCO2, when correlated with an index of ventilation (VI = mean airway pressure X respiratory rate) and confirmed by postmortem analysis of the lung. Those infants with PaCO2 greater than 40 mm Hg before surgery had a 77% mortality; when PaCO2 reduction could be achieved only with VI greater than 1000, the mortality was still greater than 50%. After repair, however, the ability to hyperventilate to PaCO2 less than 40 mm Hg proved to be an important determinant of survival; only one of 31 infants in this group died, whereas only two of 27 infants with PaCO2 greater than 40 mm Hg survived. In 16 infants with PaCO2 greater than 40 mm Hg despite hyperventilation, high-frequency oscillatory ventilation was started. This resulted in a rapid fall in PaCO2, but 14 of the 16 infants had only temporary improvement in oxygenation, and died. In five of the infants who died, alveolar number was assessed by postmortem morphometric analysis; there was a severe reduction to less than 10% of published normal neonatal values. Pulmonary vascular changes of increased muscularization were less remarkable than those observed in infants with persistent pulmonary hypertension. Our findings suggest that the degree of pulmonary hypoplasia (which would not be influenced by surgical repair), rather than the pulmonary vascular abnormality, mainly determines survival. Consideration could therefore be given to an initial nonsurgical approach to congenital diaphragmatic hernia, with the expectation that pulmonary function might improve and pulmonary vascular resistance decrease.

Hernia, Diaphragmatic↗

PubMed1987

Effect of surgical repair on respiratory mechanics in congenital diaphragmatic hernia.

To determine whether surgical repair of congenital diaphragmatic hernia (CHD) results in improvement in respiratory mechanics, we measured respiratory system compliance in nine patients (five survivors and four nonsurvivors) before and after operation. In all nine infants, CHD was diagnosed within 6 hours of life, and surgical repair was through an abdominal approach after a period of stabilization. Measurements were made noninvasively, using the passive expiratory flow-volume technique. In only one of the nine infants did compliance immediately improve after surgical repair, and in another it showed no change. Both of these infants survived, with an uneventful postoperative course. In the remaining seven infants, however, postoperative compliance immediately decreased to 10% to 77% from the preoperative value. The four infants with more than 50% decrease in compliance died with increasing hypoxemia and acidosis. These results suggest that respiratory mechanics in CHD, far from improving, frequently deteriorate as a result of repair of the hernia. The role of urgent surgery in this malformation should be reevaluated.

Hernia, Diaphragmatic↗

PubMed1987

Molecular cloning of cDNAs of human liver and placenta NADH-cytochrome b5 reductase.

A cDNA coding for human liver NADH-cytochrome b5 reductase (cytochrome b5 reductase, EC 1.6.2.2) was cloned from a human liver cDNA library constructed in phage lambda gt11. The library was screened by using an affinity-purified rabbit antibody against NADH-cytochrome b5 reductase of human erythrocytes. A cDNA about 1.3 kilobase pairs long was isolated. By using the cDNA as a probe, another cDNA (pb5R141) of 1817 base pairs was isolated that hybridized with a synthetic oligonucleotide encoding Pro-Asp-Ile-Lys-Tyr-Pro, derived from the amino acid sequence at the amino-terminal region of the enzyme from human erythrocytes. Furthermore, by using the pb5R141 as a probe, cDNA clones having more 5' sequence were isolated from a human placenta cDNA library. The amino acid sequences deduced from the nucleotide sequences of these cDNA clones overlapped each other and consisted of a sequence that completely coincides with that of human erythrocytes and a sequence of 19 amino acid residues extended at the amino-terminal side. The latter sequence closely resembles that of the membrane-binding domain of steer liver microsomal enzyme.

Amino Acid Sequence↗

PubMed1987

Structural comparison of bovine erythrocyte, brain, and liver NADH-cytochrome b5 reductase by HPLC mapping.

NADH-cytochrome b5 reductases purified from bovine erythrocytes and from bovine brain and liver microsomes solubilized with lysosomal protease were subjected to structural analysis by using HPLC mapping, amino acid analysis of the resulting peptides, and NH2-terminal sequence analysis of apoproteins. HPLC maps of the tryptic peptides derived from these enzymes were very similar to each other, and amino acid analysis of the HPLC-separated peptides indicated that the structures of these enzymes are identical except for the NH2-terminal region. The NH2-terminal sequence of the brain enzyme determined by automated Edman degradation was as follows: NH2-Phe-Gln-Arg-Ser-Thr-Pro-Ala-Ile-Thr-Leu-Glu-Asn-Pro-Asp- Ile-Lys-Tyr-Pro-Leu-Arg-Leu-Ile-Asp-Lys-Glu-Val-Ile- This sequence is identical to that of liver enzyme except that the liver enzyme started at the 3rd Arg or 4th Ser. The NH2-terminal amino acid residue of the soluble erythrocyte enzyme was not detected by automated Edman degradation. The sequence analysis of a tryptic peptide from the erythrocyte enzyme indicated that Leu is present before the NH2-terminal Phe of the brain enzyme. The recently reported sequence of the apparently identical protein (Ozols et al. (1985) J. Biol. Chem. 260, 11953-11961) differs in two amino acid assignments from our sequence.

Amino Acid Sequence↗

PubMed1987

A search for endogenous Na+,K+-ATPase inhibitor in acutely volume-expanded hog plasma led to lysophosphatidylcholine gamma-stearoyl.

An Na+,K+-ATPase inhibitor possessing inhibitory activity against the specific binding of ouabain to Na+,K+-ATPase has been purified from the plasma of acutely saline-infused hogs. The purification was performed by a combination of Amberlite XAD-2 adsorption chromatography and five steps of high-pressure liquid chromatography (HPLC). Fast atom bombardment mass and proton nuclear magnetic resonance (NMR) spectrometric studies identified the purified substance as lysophosphatidylcholine gamma-stearoyl (LPCS). The ouabain-displacing activity in plasma, due to this compound, increased with time during saline infusion. The maximal level reached was approximately 12 times higher than that in the pre-infusion plasma sample. Lysophosphatidylcholines (LPCs) containing myristoyl, palmitoyl and oleoyl groups were also inhibitory to Na+,K+-ATPase and ouabain-binding to the enzyme. These LPCs were effective at 100 mumol/l concentrations in attaining 50% inhibition of the enzyme activity and ouabain-binding activity of Na+,K+-ATPase. These results suggest that LPCs containing long chain fatty acids could play an important role as a Na+,K+-ATPase inhibitors under volume-expanded conditions.

Animals↗

PubMed1987

Role of T lymphocyte subsets in protection and recovery from Hantaan virus infection in mice.

Adult athymic nude (BALB/c background) mice or inbred BALB/c mice were inoculated intraperitoneally with Hantaan virus (HV), and attempts were made to isolate the virus from brain, lung and spleen. Virus was isolated from the organs of BALB/c mice for only a short time after infection but was isolated from various organs of nude mice consistently for at least 84 days after infection. Viral antigen was also detected in various organs of nude mice for a long time after infection. The effects of adoptive transfer of immune serum or immune T cells from BALB/c to nude mice before or after virus inoculation were examined. Before transfer, the T cell fraction was treated with complement (C') (group 1), anti-L3T4 + C' (group 2), anti-Lyt1.2 + C' (group 3) or anti-Lyt2.2 + C' (group 4). When transferred before virus inoculation to test the effects on protection against infection, immune serum and T cells of groups 1, 2 and 4 were effective. When transferred after HV inoculation to test the effects on clearance of virus, group 1 was the most effective followed by group 2. These results suggest that humoral and cellular immunity both have roles in protection against HV infection, and that T cells possessing L3T4- Lyt2+ markers on the cell-surface are especially important for elimination of infectious virus in vivo.

Animals↗

PubMed1987

Protective effect of human granulocyte colony-stimulating factor on microbial infection in neutropenic mice.

A purified human granulocyte colony-stimulating factor (hG-CSF) was studied for its protective effect on the induction of neutropenia and enhanced susceptibility to microbial infections in mice receiving cyclophosphamide (CPA). A severe reduction in peripheral blood neutrophils was induced 4 days after injection with 200 mg of CPA per kg although the level normalized rapidly thereafter. When mice were injected subcutaneously once a day with 2.5 micrograms of hG-CSF beginning on the day after CPA injection, the reduction was prevented markedly, even 4 days later. On the other hand, in mice receiving CPA 4 days prior to infection, a weakened resistance to intraperitoneal challenge with a strain of Pseudomonas aeruginosa was induced. This weakened resistance was dose-dependently restored to normal by four daily injections with hG-CSF. A daily dose of 1.0 microgram was required for complete restoration, although hG-CSF did not directly inhibit bacterial growth in vitro. In hG-CSF-treated mice, morphologically mature neutrophils migrated rapidly into the peritoneal cavities where bacteria were inoculated, followed by a rapid elimination of bacteria from the locality as compared with controls. In addition, the same treatment with hG-CSF was able to protect significantly against systemic infections caused by Serratia marcescens, Escherichia coli, Staphylococcus aureus, and Candida albicans. These data show the possibility that prophylactic therapy with hG-CSF may augment the resistance of immunocompromised patients to infections.

Agranulocytosis↗

PubMed1987

[D-Phe12]bombesin analogues: a new class of bombesin receptor antagonists.

Previous attempts to develop analogues of bombesin that function as specific receptor antagonists have been unsuccessful. Alteration of the histidine in luteinizing hormone releasing factor has resulted in analogues that function as competitive antagonists. In the present study we have used a similar strategy and altered the histidine in bombesin. [D-Phe12]bombesin, [D-Phe12,Leu14]bombesin, and [Tyr4,D-Phe12]bombesin did not stimulate amylase release from guinea pig pancreatic acini when present alone, but each analogue inhibited bombesin-stimulated secretion. For each analogue, detectable inhibition occurred at 1 microM and half-maximal inhibition at 4 microM. Each analogue inhibited amylase release by bombesin and other agonists that stimulate secretion by interacting with bombesin receptors. The analogues of bombesin did not alter stimulation by substance P or other agonists that interact with other receptors. The inhibition of the action of bombesin was competitive with Schild plots having slopes of 1.0. Each analogue also inhibited binding of 125I-labeled [Tyr4]bombesin but not 125I-labeled substance P. These results demonstrate that [D-Phe12] analogues of bombesin function as bombesin receptor antagonists and are the only bombesin receptor antagonists that interact only with the bombesin receptor. Because of their specificity, these analogues may prove useful for defining the role of bombesin in various physiological or pathological processes.

Amino Acid Sequence↗

PubMed1987

Heat-treated factor VIII/von Willebrand factor concentrate in platelet-type von Willebrand's disease.

Cryoprecipitate has proved to correct the hemostatic defects in von Willebrand's disease (vWD) and platelet-type vWD. However, recent studies have revealed that transmission of the AIDS retrovirus (HIV) occurs through exposure to blood products including cryoprecipitate. Treatment with heat-treated factor VIII/von Willebrand factor (vWf) concentrates may have certain advantages over treatment with nonheated products, if these preparations are efficacious in these disorders. We found that a commercially available factor VIII/vWf concentrate, Haemate P, contained the high-molecular-weight multimers of vWf and had a ratio of ristocetin cofactor (RCof) to vWf antigen (vWf:Ag) close to unity. In addition, its capacity to directly induce aggregation of platelet-type vWD platelets in vitro was similar to that for cryoprecipitate. When infused into a patient with platelet-type vWD, Haemate P shortened the prolonged bleeding time and caused spontaneous platelet aggregation in vitro with a mild diminution of platelet count. These results indicate that some of the heat-treated factor VIII/vWf concentrates may provide a safer, yet still effective, treatment for platelet-type vWD.

Factor VIII↗

PubMed1987

Identification of Na+,K+-ATPase inhibitors of volume-expanded hog plasma.

Na+,K+-adenosine triphosphatase (ATPase) inhibitors possessing inhibitory activities against the specific binding of ouabain to Na+,K+-ATPase and 86Rb uptake into hog erythrocytes have been purified from the plasma of hog acutely infused with saline. The purifications were performed by a combination of Amberlite XAD-2 adsorption chromatography and several steps of high performance liquid chromatography using four different types of columns. Inhibitors purified to homogeneity were identified as linoleic and oleic acids, gamma-stearoyllysophosphatidylcholine, gamma-arachidoyllysophosphatidylcholine, gamma-linoleoyllysophosphatidylcholine, and gamma-oleoyllysophosphatidylcholine. Small amounts of beta-arachidoyllysophosphatidylcholine, gamma-docosapentaenoyllysophosphatidylcholine, gamma-eicosatrienoyllysophosphatidylcholine, and gamma-palmitoyllysophosphatidylcholine were also detected by both fast atom bombardment mass and proton nuclear magnetic resonance spectrometric studies. Only gamma-acyllysophosphatidylcholines showed inhibitory activities on Na+,K+-ATPase and ouabain-binding activities. These lysophosphatidylcholines and unsaturated free fatty acids were effective at 100 microM levels in attaining 50% inhibition of the enzyme activity. The ouabain-displacing activity in plasma caused by these compounds increased with time during saline infusion. The maximal plasma levels of these components were approximately 10 times higher than that in the preinfusion plasma sample.

Animals↗

PubMed1987

Effects of mitomycin C, 5-fluorouracil and cyclophosphamide on drug absorption, enzyme activities and mucosal lipid composition of intestine.

The effect of a single intravenous or oral administration of mitomycin C (MMC), 5-fluorouracil (5-FU) or cyclophosphamide (CP) on drug absorption was studied in rats in relation to changes in membrane characteristics. At 48 h after pretreatment, a differential effect on the absorption of sulfanilamide and L-tryptophan was observed in in situ recirculation experiments. Intravenous MMC administration suppressed the absorption of both sulfanilamide and L-tryptophan to a similar extent as a higher oral dose of this agent. Dosing with 5-FU via both routes caused the largest but almost equal suppression of L-tryptophan absorption. However, CP had no effect on the absorption of the two drugs. Differences in these effects were considered to reflect their pharmacological and pharmacokinetic properties. Absorption of drugs from the small intestine had a positive correlation with small intestinal wet weight regardless of the antitumor drug used, pretreatment doses and routes of administration and the results indicated that the change in absorptive surface area played a major role in this phenomenon. Toxicity to intestinal mucosa was shown to derive from an effect on dividing cells in the crypts because MMC and 5-FU preferentially decreased thymidine kinase activity. However, at the membrane level, increased mucosal membrane permeability was also confirmed by measuring the release rates of D-glucose from liposomes consisting of mucosal total lipids obtained from the antitumor drug-treated rats. Pretreatment with lipophilic and polymeric prodrugs of MMC did not exhibit any effect on drug absorption and thus, the possibility of alleviation of toxicity and adverse reactions via the prodrug approach was suggested.

Animals↗