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Biomedical subjects

R R Baker

Publications and source records attributed to R R Baker.

At least 19 recordsLinked to original sources
PubMed1992

The hydrolysis of natural phosphatidylethanolamines by phospholipase A2 from rat serum: a degree of selectivity is shown for docosahexaenoate release.

The selectivity of phospholipase A2 from serum was evaluated using radioassays and mass analyses of fatty acids liberated from phosphatidylcholine and phosphatidylethanolamine. These natural phospholipid substrates were labelled at the sn-2 position with radioactive oleate, linoleate and arachidonate. The rates of release of fatty acids were compared with their abundance at the sn-2 position of these phospholipid substrates. While there was little or no selectivity in the liberation of these fatty acids from phosphatidylcholine, there was some evidence for a preferential release of arachidonate with respect to linoleate from phosphatidylethanolamine. Mass analyses of free fatty acid products revealed that docosahexaenoate was consistently liberated at levels that exceeded its abundance at the sn-2 position of phosphatidylethanolamine. Three different, natural phosphatidylethanolamines with varying levels of docosahexaenoate showed a 1.2-1.8-fold enrichment of this polyunsaturate in the free fatty acid products compared with its abundance at the sn-2 position. This preference could also be shown when phosphatidylethanolamine was mixed with synthetic phosphatidylcholine as co-sonicated substrates. This preferential release of docosahexaenoate by serum phospholipase A2 is of considerable significance in the nervous system which is enriched in this polyunsaturate. The potential competition between liberated docosahexaenoate and arachidonate may be of fundamental importance in the response of brain to hemorrhage.

Animals↗
PubMed1992

Quantitation of alveolar distribution of liposome-entrapped antioxidant enzymes.

Liposome-encapsulated Cu,Zn superoxide dismutase (Cu,Zn SOD) and catalase (CAT) were instilled intratracheally in rabbits, and the temporal and spatial distribution of Cu,Zn SOD and CAT within the lung was assessed at the organ and cellular levels. Specific activities of Cu,Zn SOD and CAT were increased in both lung homogenates and isolated alveolar type II pneumocytes. Peak Cu,Zn SOD activities in lung homogenates and alveolar type II cells were observed 4 h after liposome instillation and returned to control levels by 24 h, whereas CAT activities remained significantly above controls. There were no significant differences in liposome distribution or antioxidant enzyme uptake among lung lobes. The distribution of fluorescently labeled Cu,Zn SOD and CAT was assessed with the use of epifluorescence microscopy and digital image processing to determine patterns of cellular incorporation of liposome-entrapped Cu,Zn SOD and CAT within the lung. Although the mean fluorescence intensity of alveoli from rabbits instilled with liposomes containing labeled Cu,Zn SOD and CAT was greater than autofluorescence observed with either no liposome or empty liposome instillation, fluorescence intensity varied between adjacent alveoli. Both fluorescently labeled Cu,Zn SOD and CAT were located cytosolically, and uptake was not limited to alveolar type II pneumocytes. These results demonstrate that a single intratracheal instillation of liposomes can effect increases in Cu,Zn SOD and CAT activities in distal lung cells, including alveolar type I and type II cells and macrophages.

Animals↗
PubMed1992

The management of breast cancer with immediate or delayed reconstruction.

In patients with stage I and stage II disease who are candidates for a mastectomy, either immediate or delayed reconstruction can be accomplished with remarkably good cosmetic results. Age is not a specific contraindication to reconstruction, but, in my experience, the majority of women over 55 years of age are not interested. Mastectomy or modified radical mastectomy should be performed in these patients using a technique that facilitates delayed reconstruction. The patient may or may not elect to have the reconstruction eventually. Immediate or delayed reconstruction is appealing to a significant number of women under 55 years of age. They should see a plastic surgeon in consultation and the advantages and disadvantages of a subpectoral silicone implant vs. a myocutaneous flap (usually a transverse rectus abdominis musculocutaneous flap) should be discussed in detail. The patient's acceptance of the cosmetic result is better if she has an opportunity preoperatively to review photographs of reconstructed breasts and to discuss the results with women who have undergone a similar procedure. The timing of the reconstruction is a matter of clinical judgment; no prospective clinical trials have been performed. Immediate reconstruction is feasible if the skin flaps will accept the slight tension produced by either a subpectoral implant or a transposed muscle flap. A subpectoral silicone implant produces a satisfactory cosmetic result in the majority of patients, particularly if both breasts are supported by a properly fitting brassiere. In long-term follow-up, infection, contracture, and displacement requiring removal and reinsertion occur in approximately 15% of patients. Reconstruction by a myocutaneous flap is a technically more difficult operation. The operating time is prolonged significantly and blood loss is increased. In my opinion, a myocutaneous flap probably is not worth the risk of a heterologous transfusion. The long-term cosmetic results, however, are considerably better in comparison to a subpectoral silicone implant. The reconstructed breast is much more mobile, making it a more realistic replacement of the original breast. In most cases, it is better to perform this type of reconstruction with a myocutaneous flap as a delayed procedure. In experienced hands, however, immediate reconstruction, with the transverse rectus abdominis musculocutaneous flap harvested while the modified radical mastectomy is being performed, is perfectly feasible. Nipple/areolar reconstruction is available. However, the cosmetic results are only fair to good, and the patient should be aware of this before undergoing the procedure. The problem of symmetry between the breasts requires a good deal of judgment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Mechanisms of H2O2-mediated injury to type II cell surfactant metabolism and protection with PEG-catalase.

Alterations in type II pneumocyte function, including surfactant biosynthesis, may play a significant role in the development and pathophysiology of oxidant-induced lung injury. The results of this study showed that type II cells exposed to 50-300 microM H2O2 demonstrated a dose-dependent decrease in phosphatidylcholine (PC) synthesis with only minimal changes in cell viability. The activities of the choline-phosphate cytidyltransferase and cholinephosphotransferase, specific enzymes of PC synthesis, were not significantly decreased by the exposure. However, the activity of glycerol-3-phosphate acyltransferase, a sulfhydryl-dependent enzyme involved in an early stage of phospholipid synthesis, was decreased by the exposures in a manner that was similar to that seen for PC synthesis. Further studies showed that incubation of type II cells with polyethylene glycol-conjugated catalase for 1 h resulted in an increase in the cell-associated catalase activity (53 +/- 5 vs. 6.7 +/- 1.5 units/mg protein for controls). Confocal microscopy analysis showed that a significant portion of this activity was located intracellularly. More importantly, these cells were protected from changes in PC synthesis rates when subsequently incubated with 300 microM H2O2. These results indicate that the deleterious effects of H2O2 on type II cell surfactant synthesis may be pharmacologically modified in vitro, a concept that may have utility with regard to the modulation of in vivo lung injuries.

Animals↗
PubMed1990

Phosphatidylinositol synthetase activities in neuronal nuclei and microsomal fractions isolated from immature rabbit cerebral cortex.

The synthesis of phosphatidylinositol was studied using a nuclear fraction N1, a microsomal fraction P3, rough (R) and smooth (S) microsomal fractions and a microsomal fraction P derived from isolated nerve cell bodies. Each fraction was prepared using cerebral cortices of 15-day-old rabbits. In assays using CDP-diacylglycerol (prepared from egg phosphatidylcholine) and myo[3H]inositol at pH 7.4, fraction N1 had the highest maximal specific rates of phosphatidylinositol synthetase (EC 2.7.8.11) (expressed per mumol phospholipid in the fraction). However the three microsomal fractions achieved maximal specific activities at liponucleotide concentrations close to 50 microM, while fraction N1 required 200 microM concentrations. In certain cases (25-120 microM CDP-diacylglycerol, and at higher pH values) fraction R had specific activities which equalled or surpassed those of N1. However, with respect to inositol, fraction N1 had a distinctly lower Km than was shown for fractions R or P3. Each of the microsomal fractions and N1 required Mg2+ for the reaction, but for N1, maximal rates could be sustained at 0.1 mM, while for the microsomal fractions the optimal Mg2+ concentration was 1 mM. For each fraction Mn2+ could not replace Mg2+ in the reaction and Mn2+ was inhibitory. The optimal pH for the reaction was between 8.0 and 9.0. Phosphatidylinositol synthetase could also be shown using fraction N1 enriched in endogenous CDP-diacylglycerol. The relatively high specific activities of fraction N1, and the differences found between N1 and the microsomal fractions, for optimal CDP-diacylglycerol and Mg2+ concentrations and for Km values for inositol, support the existence of a neuronal nuclear phosphatidylinositol synthetase.

Animals↗
PubMed1990

The eicosanoids: a historical overview.

Eicosanoids are biologically active compounds derived from 20 carbon unsaturated fatty acids, among which arachidonic acid is a substrate of particular importance. The history of the eicosanoids dates back to the thirties, when new biologically active compounds were found in human seminal plasma. These "prostaglandins" were purified, and their structures and mechanisms of biosynthesis were elucidated in the early sixties. Other eicosanoids, including thromboxane A2, a potent platelet aggregating agent, and prostacyclin, an antagonist to thromboxane A2, were discovered in the seventies. The inhibitory actions of acetylsalicylic acid on eicosanoid synthesis were also uncovered at this time. In 1979, a new metabolic sequence leading to the synthesis of a new group of eicosanoids, called leukotrienes, was reported. The leukotrienes have several biological activities, including the mediation of bronchoconstriction in allergic response. The eicosanoids comprise a diverse group of biologically active compounds; many of these arise from arachidonic acid, and are associated with injury, allergic responses, and platelet aggregation.

Eicosanoids↗
PubMed1990

Unusual lesions and their management.

Treatment of a breast lesion should never be undertaken without a precise histologic diagnosis, which means careful examination of multiple sections of tissue embedded in paraffin and appropriately stained. The author described the clinical and histologic features of lobular and medullary cancers; cystosarcoma phylloides; carcinosarcoma; Paget's disease; adenoid cystic carcinoma; mucinous, tubular, and papillary cancers; and other unusual lesions that can originate elsewhere in the body. For each, treatment suggestions are offered.

Adenocarcinoma↗
PubMed1990

Fatty acid release in incubations of serum with synaptosome and myelin subfractions of brain.

To study lipid breakdown in brain membranes following hemorrhage, synaptosome and myelin fractions isolated from rat brain were incubated with rat serum. After 3 h in vitro at 37 degrees C, 0.43 and 0.26 mumol of fatty acid were released in incubations containing synaptosomes (1.37 mumols phospholipid) or myelin (1.23 mumols phospholipid), respectively, in the presence of 0.25 mL serum. Less than 0.05 mumol of fatty acid was liberated in incubations containing only serum, synaptosomes, or myelin. For synaptosomes and serum, docosahexaenoate was the principal fatty acid released (28 mol% of total) after 3 h of incubation. This fatty acid and arachidonate made up 43 mol% of the liberated fatty acid. The presence of free docosahexaenoate was of interest, as this fatty acid is particularly enriched in phosphatidylserine and phosphatidylethanolamine, phospholipids found in the cytoplasmic half of the synaptosomal plasma membrane and in interior synaptosomal membranes. In incubations of serum and myelin, oleate was the major free fatty acid produced in 30 min to 3 h of incubation (29-35 mol% of total). After 3 h, docosahexaenoate contributed 20 mol% to the total. The release of fatty acids from the membranes may be mediated by serum phospholipase(s) or possibly by activated endogenous lipolytic activities.

Animals↗
PubMed1990

The acylation of 1-acyl-sn-glycero-3-phosphate by neuronal nuclei and microsomal fractions of immature rabbit cerebral cortex.

The acylation of 1-acyl-sn-glycero-3-phosphate to form phosphatidic acid was studied using a neuronal nuclear fraction N1 and microsomal fractions P3, R (rough), S (smooth), and P (neuronal microsomes from nerve cell bodies) isolated from cerebral cortices of 15-day-old rabbits. The assays contained this lysophospholipid, ATP, CoA, MgCl2, NaF, dithiothreitol, and radioactive palmitate, oleate, or arachidonate. Of the subfractions, N1 and R had the highest specific activities (expressed per micromole phospholipid in the fraction). The rates with oleate were two to four times the values seen for phosphatidic acid formation from sn-[3H]glycero-3-phosphate and oleoyl-CoA. Using oleate or palmitate, fraction R had superior specific rates to N1 at low lysophosphatidic acid concentrations. With increasing lysophospholipid concentrations the specific rates of N1 and R came closer together and maintained at least a twofold superiority over fraction P. Fraction S had the lowest specific rates of phosphatidic acid formation. Fractions N1, R, and P showed a preference for palmitate and oleate over arachidonate, particularly at low concentrations of lysophosphatidic acid. For N1 and R, the preference was also more marked at higher concentrations of fatty acid. Thus a selectivity for saturated and monounsaturated fatty acids was shown in the formation of phosphatidic acid, as was a concentration of acylating activity in the neuronal nucleus and the rough endoplasmic reticulum.

Acylation↗
PubMed1990

Endogenous xanthine oxidase-derived O2 metabolites inhibit surfactant metabolism.

The ability of xanthine oxidase (XO)-derived, partially reduced O2 species (PROS) to inhibit surfactant production was examined in freshly isolated alveolar type II (ATII) pneumocytes from New Zealand White rabbits. [Methyl-3H]choline chloride and [1-14C]palmitate incorporation into phosphatidylcholine (PC) decreased in a dose-dependent manner, whereas peak media hydrogen peroxide (H2O2) concentration increased, when 1, 5, or 10 mU/ml XO were added to cell suspensions containing 500 microM xanthine. Addition of 100 microM allopurinol inhibited H2O2 production and abolished the decrease in choline and palmitate incorporation into PC. ATII cells incubated with 500 microM xanthine alone incorporated choline and palmitate at 90 and 80% of control levels, respectively. However, 100 microM allopurinol restored precursor incorporation to control values. To identify a possible intracellular source of PROS, ATII cell xanthine dehydrogenase (XDH) and XO activities were measured. Both total activity (XDH + XO; 45 +/- 7 microU/mg protein) and the percentage activity in the oxidase form (%XO; 30 +/- 4%) remained unchanged in ATII cells incubated in media only (control) for 2 h. In contrast, incubation of ATII cells with 500 microM xanthine resulted in a 50% loss of XDH + XO activity and a 21% increase in %XO within 10 min. After 2 h there was no measurable XDH + XO activity in xanthine-treated cells. Total XDH + XO activity in cells incubated with 500 microM xanthine and 100 microM allopurinol was less than 6% of control values throughout the incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Allopurinol↗
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↗
PubMed1979

The isolation and lipid composition of subcellular fractions derived from neuronal perikarya isolated in bulk from rabbit cerebral cortex.

(1) Neuronal perikarya were isolated from rabbit cerebral cortex and were homogenized and separated into a number of subcellular membrane fractions using differential and discontinuous density gradient centrifugation. (2) The efficiency of homogenizing the nerve cell bodies could be greatly increased by the preliminary passage of the cell body fraction through a micropipet tip. (3) Of a number of density media, a discontinuous gradient of metrizamide gave the best resolution of the mitochondrial and lysosomal marker enzymes found in the crude mitochondrial fraction. This yielded a purified mitochondrial fraction and several lighter membrane fractions. (4) The lighter membrane fractions in metrizamide contained a degree of mitochondrial contamination which could be removed by a second gradient spin on 1.2 M sucrose, producing a second mitochondrial fraction and two light membrane fractions. (5) Based on marker analyses, fractions enriched in nuclei, mitochondria, microsomes and plasma membrane/lysosomes were produced. (6) The two mitochondrial fractions showed the highest, and the nuclear fraction the lowest specific phospholipid content. Cholesterol: phospholipid molar ratios showed a gradient of values from a low (0.2) for the mitochondria and nuclei to an intermediate value (0.4) for the microsomes to a high (0.6) for the light membrane fractions. (7) Phospholipid distributions indicated that for the nuclear and mitochondrial fractions phosphatidylinositol was more abundant than sphingomyelin or phosphatidylserine, while for the microsomes and the two light membrane fractions these three phospholipids were present in almost equal amounts.

Acetylglucosaminidase↗
PubMed1979

Selective nonoperative management of contained intrathoracic esophageal disruptions.

Eight patients with intrathoracic esophageal disruptions were managed nonoperatively and without pleural drainage. Criteria for nonoperative treatment included the following: disruption contained in the mediastinum or between the mediastinum and visceral lung pleura; drainage of the cavity back into the esophagus; minimal symptoms; and minimal signs of clinical sepsis. Cause of the esophageal perforation was pneumostatic dilatation (1 patient), vomiting (2), and a leak following esophageal operation (5). Antibiotics were administered intravenously to all patients; hyperalimentation was accomplished intravenously in 5, and nasogastric suction was used in only 1. The cavities contracted and the esophageal leaks sealed in all instances. Time before oral intake was resumed ranged from 7 to 38 days (average, 18 days). Days until discharge ranged from 15 to 52 days (average, 28 days).

Adult↗
PubMed1979

A comparison of modified radical mastectomy to radical mastectomy in the treatment of operable breast cancer.

This study compares the results of modified radical mastectomy (144 cases) to radical mastectomy (188 cases) in the treatment of operable breast cancer. Two hundred five patients had Stage I breast cancer, 60 had Stage II disease and 67 had Stage III disease (TNM System). There was no statistically significant difference in five year survival when the results of a radical mastectomy were compared to a modified radical mastectomy at any stage of disease. There was no statistically significant difference in the incidence of local recurrence in patients with Stage I and Stage II disease when the results of a radical mastectomy were compared to modified radical mastectomy. Those patients with Stage III disease who were treated by a modified radical mastectomy had a statistically significant higher incidence of local recurrence (chest wall and axilla) in comparison to patients treated by radical mastectomy. We have concluded that a modified radical mastectomy is the treatment of choice in patients with Stage I and Stage II diseases. In patients with Stage III disease, a radical mastectomy provides a better chance of local control of the disease but offers no increased chance of survival.

Breast Neoplasms↗
PubMed1979

The indications for transcervical mediastinoscopy in patients with small peripheral bronchial carcinoma.

A series of 80 patients with roentgenographic evidence of bronchial carcinomas 3 centimeters or less in size was analyzed as to the incidence of mediastinal lymph node metastases. Forty patients underwent transcervical mediastinoscopy prior to thoracotomy and 40 patients did not. Three patients with large cell undifferentiated carcinoma had mediastinal lymph node metastases which could be detected by transcervical mediastinoscopy. None of the 40 patients who did not undergo mediastinoscopy had palpable evidence of mediastinal lymph node metastases at thoracotomy. The survival rates for the two groups of patients were similar. On the basis of this study, we have concluded that mediastinal exploration is not routinely indicated in patients with peripheral T1, N1, M0 lesions.

Adenocarcinoma↗