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Biomedical subjects

R R Baker

Publications and source records attributed to R R Baker.

At least 55 records · Page 3Linked to original sources
PubMed1990

Mechanisms of extracellular hydrogen peroxide clearance by alveolar type II pneumocytes.

This study quantified the ability of freshly isolated alveolar type II (ATII) pneumocytes to reduce extracellularly produced hydrogen peroxide (H2O2) and identify the mechanisms involved. ATII cells were isolated to high purity (greater than 85%) from rabbit lungs by enzymatic digestion and Percoll centrifugation and suspended in Eagle's minimum essential medium (MEM). They were then coincubated with either 500 microM xanthine and 10 mU/ml xanthine oxidase (XO; pH 7.4; 25 degrees C) or 300 microM H2O2. The extracellular H2O2 concentration [H2O2] was measured in the following conditions over a 60-min period: 1) MEM alone, 2) untreated (control), 3) 3-amino-1,2,4-triazole (ATZ)-treated, or 4) 1-chloro-2,4-dinitrobenzene-treated ATII cells. Addition of xanthine and XO to MEM alone resulted in a time-dependent increase in [H2O2], reaching a plateau value of approximately 300 microM after 45 min. In the presence of control ATII cells (1 x 10(6) cells/ml), [H2O2] remained at control levels. When coincubated with 300 microM H2O2, ATII cells cleared H2O2 at a higher rate than an equivalent amount of free catalase. Incubation with ATZ decreased ATII cell catalase activity by 89% and significantly impaired their ability to clear H2O2 (half-life = 18.1 +/- 2.7 vs. 1.3 +/- 0.1 min, P less than 0.01). ATZ-treated cells were more susceptible to oxidant injury, as shown by their decreased ability to exclude trypan blue after 60 min of H2O2 exposure. On the other hand, glutathione-depleted cells scavenged H2O2 at the same rate as controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Amitrole↗
PubMed1990

Hemorrhagic infarction of hilar lymph nodes associated with combined heart-lung transplantation.

The histologic changes in lymph nodes transplanted during combined heart-lung transplantation were examined. We studied at autopsy nine patients who had received a total of 10 heart-lung transplants. Hemorrhagic infarction of hilar nodes was found in eight of the 10 transplanted lungs. Pulmonary parenchymal pathologic changes associated with lymph node infarction included acute rejection (two cases), chronic rejection with bronchiolitis obliterans (two cases), and pneumonia (four cases). In one of the transplants without lymph node infarction there was chronic rejection with bronchiolitis obliterans and in another there was evidence of bronchopneumonia. The hemorrhagic lymph node infarction seen in the recipients of combined heart-lung transplant's may be directly attributable to the interruption of bronchial arteries and veins by the surgical procedure. At present the possible contribution of node infarction to postoperative morbidity or mortality is unknown.

Adolescent↗
PubMed1989

The military nurse experiment in Vietnam: stress and impact.

Demographic, health, and psychosocial data from two studies are presented on military nurses assigned to Vietnam. Army nurse subjects in the first study were grouped for comparison on three major variables: assignment to Vietnam before versus after the 1968 TET Offensive, type of nursing duties performed, and years of experience as a registered nurse (RN) prior to assignment in Vietnam. The second study compared another group of Army nurses with a group of Air Force and Navy nurses also assigned to Vietnam. Army nurses with less than two years RN experience prior to their assignment were found to be more at risk for such negative outcomes as difficulty establishing personal relationships and difficulty coping with stressful situations. Stress experiences, career dissatisfaction data, and health problems of military nurses and their children are reported. Also described are positive experiences of nurses in developing personal relationships in a rewarding professional environment.

Adaptation, Psychological↗
PubMed1989

Congenital bronchopulmonary foregut malformations. Intralobar and extralobar pulmonary sequestrations communicating with the foregut.

Two unusual variants of bronchopulmonary foregut malformations are presented. The first case was that of a 12-year-old male with a history of pectus excavatum in whom severe lobar emphysema developed secondary to an intralobar pulmonary sequestration that communicated with the esophagus. This case was unusual in that foregut communications and associated congenital anomalies are generally believed to be restricted to extralobar pulmonary sequestrations. The second case was that of a 27-year-old woman with an extralobar pulmonary sequestration that communicated with the esophagus. The sequestration was unusual in that it arose in the anterior mediastinum and received the bulk of its blood supply from the pulmonary artery. The occurrence of mixed forms of pulmonary sequestrations supports the hypothesis that extralobar and intralobar sequestrations and sequestrations with foregut communication are related thoracic disorders that are best considered bronchopulmonary foregut malformations.

Abnormalities, Multiple↗
PubMed1989

The clinical management of a normal contralateral breast in patients with lobular breast cancer.

Ninety-nine patients with the diagnosis of lobular carcinoma (LC) treated between 1970 and 1981 were reviewed. Thirteen patients had a contralateral mastectomy for duct cancer (DC) before the diagnosis of LC. Ten of the remaining 86 patients (11%) had simultaneous bilateral cancers detected by either physical examination or mammography, none by blind biopsy. Three of the surviving 38 patients (7.8%) developed a contralateral cancer an average of 143 months after operation. In comparison 167 patients with DC treated during the same period of time had a 1.8% incidence of synchronous cancer but the same incidence of subsequent cancer (7%). Lobular carcinoma in situ was not a reliable marker for predicting the presence of cancers in the contralateral breast. The diagnosis of LC is not an indication for either biopsy or removal of a normal contralateral breast.

Adult↗
PubMed1989

Development of O2 tolerance in rabbits with no increase in antioxidant enzymes.

Instillation of exogenous surfactant into rabbits exposed to 100% O2 increases survival time and decreases alveolar epithelial injury. In this study we investigated whether rabbits with increased levels of endogenous pulmonary surfactant are more resistant to hyperoxia. Rabbits were exposed to 100% O2 for 64 h and then returned to room air for 8 days (preexposed). At this time, they had normal gas exchange and alveolar permeability to solute and increased levels of lavageable alveolar phospholipids compared with control rabbits breathing air (26 +/- 2 vs. 12 +/- 2 mumol/kg). Preexposed rabbits survived significantly longer than control rabbits when reexposed to 100% O2 (166 +/- 24 vs. 80 +/- 6 h; n = 7; P less than 0.05) and had significantly higher values of total lavageable phospholipids after 72 h in 100% O2 (15 +/- 2 vs. 5 +/- 2 mumol/kg). Controls developed arterial hypoxemia after 72 h in 100% O2. On the other hand, preexposed rabbits maintained arterial PO2 values greater than 100 Torr throughout the hyperoxic exposure and developed progressive respiratory acidosis. Specific activities of CuZn and Mn superoxide dismutase, catalase, and glutathione peroxidase in lung homogenates and isolated alveolar type II pneumocytes of preexposed rabbits were unchanged from those of controls before O2 reexposure and after 72 h in 100% O2. We concluded that 1) increases in pulmonary antioxidant enzyme specific activities are not necessary for the development of O2 tolerance in rabbits and 2) pulmonary surfactant may play a role in O2 adaptation.

Animals↗
PubMed1988

The formation of phosphatidic acid de novo: a comparison of activities in neuronal nuclei and microsomes isolated from immature rabbit cerebral cortex.

The formation of phosphatidic acid from sn-glycerol 3-phosphate was studied in neuronal nuclear fraction N1 and a microsomal fraction P3, isolated from cerebral cortices of 15-day-old rabbits. Two assays were used, employing dithiothreitol, MgCl2, NaF and (A) sn-glycerol 3-phosphate, [14C]oleate, ATP and CoA or (B) sn-[3H]glycerol 3-phosphate and oleoyl-CoA. In both assays fraction N1 had specific rates of phosphatidic acid labelling (expressed per mumol phospholipid in the fraction) which were 5- to 6-times the corresponding values for P3. In contrast to N1, the formation of phosphatidic acid by fraction P3 was more sensitive to inhibition at high concentrations of oleoyl-CoA and was greatly dependent upon the presence of NaF. In the absence of this salt, P3 showed decreased phosphatidate formation and increased levels of radioactive monoacylglycerols. Using cerebral cortex, rough (R) and smooth (S) microsomal fractions were prepared, as was a microsomal fraction P from isolated nerve cell bodies. P had specific rates of phosphatidic acid labelling which were 2-3 times the values for P3, but were about 50% of the N1 values. This indicates a concentration of phosphatidate synthesis in the nucleus within the nerve cell. Specific rates for fraction R were higher and were similar to those of N1. In S, P3 and R the specific rates of phosphatidic acid synthesis paralleled specific RNA contents and indicated a location for phosphatidic acid synthesis within the rough endoplasmic reticulum.

Animals↗
PubMed1988

The release of radioactive arachidonate from lipids of red blood cell membranes: properties of membrane and serum enzymatic activities.

The release of [3H]arachidonate from the phospholipids of red blood cell membranes of rats has been studied. Membranes of red cells isolated using acid-citrate-dextrose and differential centrifugation showed an endogenous release of arachidonate at pH 7.4 in the presence of CaCl2. Membranes from red cells isolated using heparin and Percoll gradient centrifugation are better substrates for serum-mediated release of arachidonate. These experiments and results with inhibitors suggest that red blood cell and serum phospholipase A2 activities are responsible for this catabolism that may provide arachidonate for subsequent biosynthesis of eicosanoids.

Animals↗
PubMed1988

Sublethal hyperoxic injury to the alveolar epithelium and the pulmonary surfactant system.

We quantified the effects of continuous exposure to 100% O2 on the development of sublethal injury to the pulmonary alveolar epithelium of rabbits. There was a progressive increase in alveolar permeability to solute after 48 h in O2, which coincided with the onset of damage to the pulmonary microvasculature. Rabbits that were exposed to 100% O2 for 64 h and returned to room air for 24 h had, in addition to increased permeability to solute, decreased phospholipid levels, decreased total lung capacity, pulmonary edema, high minimum surface tensions in their bronchoalveolar lavage, and moderate hypoxemia. Intratracheal instillation of calf lung surfactant (CLSE) significantly ameliorated the progression of hyperoxic injury by increasing alveolar phospholipid levels and thus preventing the inhibition of lung surfactant activity by plasma proteins and other high molecular weight components of alveolar edema. We concluded that the alveolar epithelium and the pulmonary microvasculature show similar sensitivity to hyperoxia and that clinical manifestations of hyperoxic lung injury may be due, at least in part, to surfactant dysfunction.

Animals↗
PubMed1987

The incorporation of fatty acids into triacylglycerols of isolated neuronal nuclear envelopes: the influence of thiol reducing reagents and chromatin.

Using [3H]arachidonate, ATP, coenzyme A, MgCl2, EGTA and CMP, triacylglycerols were labelled in an isolated neuronal nuclear fraction, N1 (from immature rabbit cerebral cortex). When the radioactive nuclear fraction N1 was subfractionated, 75% of the labelled triacylglycerol product was located in the nuclear envelope fraction, E, indicating that the fatty acid incorporation was taking place at the nuclear membrane. However, when nuclear envelope fraction E was first isolated and then incubated with radioactive fatty acid, a significant incorporation into triacylglycerol was found only when nuclear envelope fractions had been prepared in the presence of dithiothreitol or mercaptoethanol. The use of the thiol compounds during the isolation of nuclear envelope fraction E led to specific incorporation rates (based on phospholipid content) which were at best 45-56% of the corresponding values seen for the parent nuclear N1 fraction. This was seen for nuclear envelope fractions isolated by two different procedures. Specific rates for acyl-CoA synthetase and diacylglycerol generation (by cholinephosphotransferase) were measured in nuclear envelope fractions and found to be similar to specific rates for these enzymes in the nuclear N1 fraction. The deficiency in triacylglycerol labelling in nuclear envelope fractions was likely due to impaired diacylglycerol acyltransferase activity. Higher specific rates of triacylglycerol labelling (82-90% of N1 values) were seen in nuclear envelope fractions assayed very shortly after preparation and in another subfraction of nuclear fraction N1 which contained small amounts of phospholipid and high concentrations of nucleates and protein. These data suggest that triacylglycerol formation may be maintained by the presence of chromatin, while in its absence there is a loss of acylation activity in nuclear envelope fractions.

Animals↗
PubMed1987

A critical review of the use of open lung biopsy in the management of the oncologic patient with acute pulmonary infiltrates.

In a retrospective review, 28 open lung biopsies from 27 oncology patients with acute pulmonary infiltrates were evaluated. The operative complication rate was 28%, and the operative mortality 4%. Infection caused 57% of the infiltrates (16 cases); 87% of the infections were secondary to either Pneumocystis carinii or a viral infection. Two patients had bacterial pneumonia. Sixteen of these cases survived (37%). All but one survivor had Pneumocystis carinii. A nonspecific pneumonitis either with or without associated fibrosis caused 39% of the infiltrates (11 cases). Four of these patients survived (36%). Two patients had histologic evidence of residual tumor, one secondary to leukemia and the other to a lymphoma. One of these patients who also had Pneumocystis carinii survived. This study confirms the results of several other studies. Open lung biopsy in the oncology patient with an acute pulmonary infiltrate rarely establishes the presence of a treatable lesion other than Pneumocystis carinii, a diagnosis that can usually be established by bronchoscopy. The indications for open lung biopsy are therefore limited.

Acute Disease↗
PubMed1987

The release of radioactive arachidonate from lipids of red blood cells during prolonged incubations in vitro.

Red blood cells were isolated from rat blood and incubated in the presence of [3H]arachidonate. A sizeable quantity (18%) of the radioactivity was incorporated into red cell lipids, of which phosphatidylcholine was the most highly labelled. Radioactive arachidonate was found at position 2 of this phospholipid. Free fatty acids were removed by washing the cells in solutions containing fatty-acid-free bovine serum albumin. The labelled red cells were then incubated for up to 16 h at 37 degrees C. After 16 h of incubation in saline-buffer-glucose or rat serum, 20 and 26%, respectively, of the total radioactivity was found in free fatty acids, and there were corresponding declines in the percentage radioactivities found in phosphatidylcholine. In the presence of serum, there was a more rapid release of radioactive fatty acid over the 2- to 16-h time course. There was not a significant drop in the phosphate levels of the total red cell phospholipids or phosphatidylcholine after 16 h of incubation and, as a result, there were large declines in the specific radioactivities of phosphatidylcholine. Diacylglycerols were not highly labelled and the action of phospholipase A2 on labelled phosphatidylcholine was indicated. When white blood cells were added to labelled red cells, there was little evidence of white cell involvement in the release of radioactive fatty acid, suggesting that the red cells themselves may be involved in arachidonate release. Red cells may serve as sources of arachidonate, released following hemorrhage in brain and metabolized to form various biologically active eicosanoids.

Animals↗
PubMed1987

The role of surgery in the management of selected patients with small-cell carcinoma of the lung.

This study was designed to evaluate the efficacy of surgical resection of the primary tumor and lymph nodes in patients with localized small-cell carcinoma who had responded to induction chemotherapy. The study was performed in 37 patients who received two cycles of chemotherapy consisting of cyclophosphamide, doxorubicin, and etoposide. Those patients who achieved a complete or partial (greater than 50%) response were evaluated for thoracotomy and the primary tumor and regional lymph nodes excised when feasible. Postoperatively, the patients received prophylactic cranial irradiation and were maintained on the same chemotherapy for an average of 11 months. Twelve patients were resected and found to have residual small-cell carcinoma in the operative specimen (ten) or no residual disease (two). Seven of these patients (58%) are alive without evidence of disease (median follow-up, 24 months). Seven other patients who were resected proved to have either residual foci or small-cell carcinoma mixed with adenocarcinoma or large-cell carcinoma (four) or only focal areas of adenocarcinoma, large-cell carcinoma, or squamous-cell carcinoma with no evidence of residual small-cell carcinoma. Five of these patients (71%) are alive without evidence of disease (median follow-up, 36 months). Two of the 16 patients who were not resected but treated with chemotherapy and radiation are alive at 15 and 31 months without evidence of disease, the other 14 are dead of disease.

Adult↗
PubMed1986

A comparison of the acylation of 1-acyl-sn-glycero-3-phosphoinositol and 1-acyl-sn-glycero-3-phosphocholine in neuronal nuclei in vitro using radioactive arachidonate and oleate.

A neuronal nuclear fraction (N1) was isolated from cerebral cortices of 15-day-old rabbits. Samples of N1 were incubated with a radioactive fatty acid ([3H]arachidonate or [14C]oleate), acylation cofactors, and 1-acyl-sn-glycero-3-phosphoinositol (1-acyl-GPI) or 1-acyl-sn-glycero-3-phosphocholine (1-acyl-GPC). In competition studies, both radioactive fatty acids were incubated with one lysophospholipid or the two lysophospholipids were incubated with one radioactive fatty acid. Using [3H] arachidonate and one lysophosphoglyceride, a maximal rate of incorporation into phosphatidylinositol (PI) was found at a relatively low concentration of 1-acyl-GPI (10 microM), while increasing rates of incorporation into phosphatidylcholine (PC) were seen with increasing concentrations of 1-acyl-GPC (to 65 microM). At low concentrations of lysophosphoglyceride (less than or equal to 25 microM) the rate of arachidonate incorporation into PI greatly exceeded rates of arachidonate incorporation into PC. This higher rate of arachidonate incorporation into PI was also seen in incubations where both lysophospholipids were present. For oleate, greater rates of incorporation into PC were found in comparison with rates of labelling of PI in assays using relatively high concentrations of one or both lysophospholipids. When comparing arachidonate and oleate, in assays with one or both fatty acids, the polyunsaturate showed at least threefold higher rates of incorporation into PI. For PC labelling higher rates of arachidonate incorporation were evident at the higher concentrations of 1-acyl-GPC and the superiority over oleate was not as marked as that seen in PI labelling.

Acylation↗
PubMed1986

The effects of pH, buffers, and fatty acid concentration on the incorporation of radioactive arachidonate into endogenous neuronal nuclear lipids.

Using neuronal nuclei (N1) isolated from cerebral cortices of 15-day-old rabbits the incorporation of [3H]arachidonate into N1 lipids was followed in vitro. Arachidonate was principally incorporated into triacylglycerol and phosphatidylinositol. When low concentrations (32 mM) of Tris-HC1 (pH 7.4) were used, rates of total arachidonate incorporation were small and phosphatidylinositol received the bulk (greater than 84%) of the arachidonate. When the concentration of Tris-HC1 (pH 7.4) or, in certain cases, the concentration of arachidonate was increased, there was a rise in total arachidonate incorporation into N1, with an increasing proportion of radioactivity entering triacylglycerol until it was the predominantly labelled lipid. Using other buffers (phosphate, imidazole, HEPES, pH 7.4), the shift from phosphatidylinositol to triacylglycerol as principal labelled lipid, with buffer concentration, was not as marked as with Tris-HC1 (pH 7.4). When the buffer concentration was maintained at 107 mM and the pH was lowered to 6.5, the three amine-containing buffers showed a sizeable decline in arachidonate incorporation into N1 lipids and a corresponding decrease in triacylglycerol labelling. The proportion of the total radioactivity in N1 phosphatidylinositol rose as the pH declined. Of the buffers used, Tris-HC1 showed the greatest changes over the pH range. Based upon pK values for the amine buffers, it is suggested that an increased proportion of the protonated amine may be inhibitory to arachidonate incorporation in N1. Studies of acyl-CoA synthetase in N1 indicated this enzyme as the site of the inhibition.

Animals↗
PubMed1985

The CMP-stimulated production of diacylglycerol and CDPdiacylglycerol in neuronal nuclei labelled with radioactive arachidonate.

A neuronal nuclear fraction (N1), isolated from immature rabbit cerebral cortex, was preincubated with [3H]arachidonate, ATP, CoA, Mg2+ and 1-acyl-sn-glycero-3-phosphocholine or 1-acyl-sn-glycero-3-phosphoinositol. Using the former lysophospholipid, a sizeable incorporation of radioactivity was seen in N1 phosphatidylcholine. In subsequent incubations in the presence of CMP and EGTA, there was a generation of radioactive diacylglycerol in N1 and a corresponding decline in phosphatidylcholine radioactivity. Both these changes could be blocked by the addition of CDPcholine. In incubations using N1 phosphatidylinositol or phosphatidylethanolamine prelabelled with [3H]arachidonate, no evidence was found to support a direct generation of diacylglycerol from these phospholipids. The back reaction of cholinephosphotransferase in N1 is likely the principal source of diacylglycerols bearing arachidonate. Using either lysophospholipid in the preincubations described in the opening sentence, more than half of the incorporated radioactivity derived from [3H]arachidonate was found in N1 phosphatidylinositol. In subsequent incubations with EGTA and CMP there was a production of radioactive CDPdiacylglycerol and a decline in radioactive phosphatidylinositol. Both events could be blocked by the presence of myo-inositol. Radioactive CDPdiacylglycerol, produced in N1 in the presence of CMP and EGTA, was converted back into phosphatidylinositol by the addition of myo-inositol. The production of CDPdiacylglycerol is likely the result of the back reaction of CDPdiacylglycerol:inositol phosphatidate transferase in N1.

Animals↗
PubMed1985

New frontiers in the treatment of lung cancer.

Surgical resection still is the only significant curative approach in nonsmall cell lung cancer. Recent surgical experience indicates that a modest decrease in the death rate from bronchogenic carcinoma may occur in three general areas: (1) the detection and treatment of radiographically occult squamous cell carcinoma; (2) the combination of adjuvant chemotherapy and surgical excision in selected patients with small cell carcinoma; and (3) surgical resection and postop irradiation of patients with hilar and mediastinal lymph node metastases. At the time of diagnosis, 80 to 85% of the patients present with unresectable lung cancer. These patients may benefit from other modalities of therapy, i.e., radiotherapy, chemotherapy, or immunotherapy. Failures following radiotherapy in unresectable nonsmall cell lung cancer are due to (1) distant metastasis, (2) local region failure, and (3) local and distant failure. To increase the local control, new methods of treatment have been tried, such as hyperfractionation of radiotherapy and the use of 131I antiferritin immunoglobulin. The development of effective systemic chemotherapy is necessary to treat metastatic bronchogenic carcinoma. The response rate to chemotherapeutic agents is substantially lower in nonsmall cell carcinoma than in small cell carcinoma. Investigation is ongoing to assess the effectiveness of new antitumor drugs used alone, in combination with other drugs, or combined with other modalities for the treatment of bronchogenic carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗