Search PubMed⌕ Search

Biomedical subjects

R R Baker

Publications and source records attributed to R R Baker.

At least 73 records · Page 4Linked to original sources

The subcellular distribution of free fatty acids released during post-decapitative ischemia in rat cerebral cortex.

After periods of 5 and 30 min following decapitation, rat cerebral cortices were removed and subcellular fractions were prepared. Fractions P1A (large myelin), P1B (nuclei), P1C (cells and debris), P2A (small myelin), P2B (synaptosomes), P2C (mitochondria), and P3 (microsomes) were isolated. Free fatty acid levels of 1.0 and 1.4 mumol/g tissue were found in the homogenates at the early and late times of ischemia. In the 30-min samples, P1A, P1C, and P2A had relatively high specific contents of total free fatty acids in comparison with other subfractions. At this time P2C was relatively enriched in arachidonate, P1A and P2A were enriched in palmitate, and P2B and P3 were enriched in stearate in comparison with the homogenate. P2C had the highest ratio of polyunsaturates/saturates in its free fatty acid pool. Comparing the 5- and 30-min samples, a large increase in the quantity of free fatty acids was found in fractions P1A and P2A, so that at the later time P1A + P2A contained 60 mol% of the free fatty acid in the total subfractions derived from cerebral cortex. In comparison with the homogenate, the lack of accumulation of free fatty acids in certain membranes known to possess phospholipase activities (e.g., phospholipase A2 in P2C) and the buildup of free fatty acids in P1A and P2A led to the hypothesis that free fatty acids may be migrating outwards from intracellular sites of production and accumulating in the multilamellar structure of myelin.

Animals↗

Transthoracic needle aspiration biopsy of benign and malignant lung lesions.

Transthoracic needle aspiration biopsy (TNAB) of lung lesions is a well established procedure for diagnosing lung lesions. The emphasis in the literature has been on diagnosing malignant lesions with an accuracy rate greater than 90% frequently reported. Experience with 650 patients showed that TNAB can diagnose malignant lesions in 95% of patients with cancer, and more importantly that TNAB can identify benign lesions in 88% of patients with such lesions. In this patient population, 22% of undiagnosed, noncalcified lung lesions were benign. Therefore, TNAB of lung lesions has a potential of limiting diagnostic thoracotomies to fewer than 8% of patients with lung lesions, significantly reducing the number of unnecessary thoracotomies for benign disease. The success of TNAB is affected by equipment, technique, skill, and experience and is enhanced by close cooperation among the various physicians involved.

Aged↗

Papillary carcinoma of the thyroid gland.

The results of this analysis have demonstrated that papillary carcinoma of the thyroid gland rarely causes the death of the patient. Bilateral subtotal lobectomies, partial lobectomies and probably total lobectomy combined with contralateral partial lobectomy should not be performed in the treatment of this disease. The incidence of local recurrence is higher after these procedures, and any subsequent operative procedure is complicated by scarring secondary to the initial procedure. Total lobectomy is the procedure of choice for patients with disease confined to one lobe on palpation. Total thyroidectomy should only be performed for palpable disease in both lobes. Excision of a grossly normal contralateral lobe solely to obtain microscopic tumor which rarely becomes clinically apparent is not worth the inherent risk of bilateral recurrent palsy of the nerve or permanent hypoparathyroidism. Cervical metastasis of the lymph nodes which are detected either synchronously or during subsequent follow-up examination can almost always be resected by some type of modified neck dissection. A radical neck dissection with the resection of the jugular vein and the sternocleidomastoid muscle is rarely if ever necessary. The administration of thyroid hormone as a surgical adjuvant may not be of any benefit and its routine use is probably not necessary.

Adolescent↗

Phosphatidylcholine as a source of diacylglycerols in neuronal nuclei incubated in the presence of EGTA and CMP.

A neuronal nuclear fraction (N1), isolated from immature rabbit cerebral cortex, was preincubated with 1-[14C]palmitoyl-sn-glycero-3-phosphorylcholine and oleoyl-CoA. Most of the radioactivity was recovered in N1 phosphatidylcholine, and subsequent incubations in the presence of EGTA and CMP indicated an increase in radioactivity in N1 diacylglycerol and triacylglycerol which was matched by a decline in the labelling of N1 phosphatidylcholine. N1 phosphatidylcholine was also prelabelled using [14C]oleate and 1-acyl-sn-glycero-3-phosphorylcholine in vitro, or by intrathecal injection of [3H]oleate prior to N1 isolation. In the following incubations with EGTA and CMP there was a good correspondence between the radioactive decline in N1 phosphatidylcholine and the increase in radioactivity in N1 diacylglycerol. In all these experiments the generation of radioactive diacylglycerol depended upon the presence of EGTA and CMP in the incubations and could be largely inhibited by the addition of CDP-choline. During the prelabelling procedures noted above, other complex lipids had less of the total radioactivity than phosphatidylcholine and showed little or no decline in radioactivity in the presence of EGTA and CMP. In N1 preincubations with [14C]oleate and lysophosphatidylethanolamine, phosphatidylethanolamine could be more highly labelled than phosphatidylcholine, but in subsequent incubations with EGTA and CMP no decline was seen in phosphatidylethanolamine radioactivity. It is concluded that the back reaction of cholinephosphotransferase in N1 represents an active route for the production of diacylglycerols bearing palmitate and/or oleate.

Animals↗

Preoperative assessment of the patient with breast cancer.

The clinical assessment of patients with stage I and II breast cancer is limited to a history and physical examination supplemented by a chest radiograph and serum alkaline phosphatase determination. In the absence of positive clinical findings or elevation of the alkaline phosphatase, routine scintigraphy of the skeletal system and liver is not indicated. In contrast, routine scintigraphy of the skeletal system and liver is indicated in patients with stage III disease, even in the absence of clinical evidence of systemic metastasis.

Adult↗

Prognostic factors in surgically resected limited-stage, nonsmall cell carcinoma of the lung.

The gross pathological, microscopic, and clinical features of 173 Stage I and Stage II primary nonsmall cell carcinomas resected for cure by segmental resection, lobectomy, or pneumonectomy at the Johns Hopkins Hospital were analyzed to determine which provided useful independent prognostic information. The tumors studied included 79 squamous carcinomas (56%); 74 adenocarcinomas (44%), including 15 undifferentiated tumors which contained intracellular mucin; 18 large-cell undifferentiated carcinomas (10%); one giant cell carcinoma (less than 1%); and one adenosquamous carcinoma (less than 1%). Clinical features evaluated for each case included age, sex, race, and history of previous or subsequent malignancy; and pathologic features evaluated included tumor size, lymph node metastases, tumor location, cellular anaplasia, desmoplastic response, inflammatory response, preexisting scar, tumor necrosis, and degree of tumor differentiation. Multivariate analysis using the Cox life table regression model indicated that five features had a significant (p less than 0.05) independent association with subsequent death due to the tumor, and that the final set was highly significant (p = 0.001). These features were the following: large-cell undifferentiated histology, lymph node metastases expressed as N classification, tumor size expressed as T classification, tumor giant cells in any histologic type, and absent or minimal plasma cell infiltration. No additional prognostic information was obtained from any of the other features analyzed.

Adenocarcinoma↗

An increased incorporation of fatty acid into triacylglycerols of neuronal nuclei in vitro in the presence of CMP and EGTA.

Neuronal nuclei (N1) were isolated from cerebral cortices of 15-day-old rabbits. With the addition of both EGTA and CMP the incorporation of radioactive oleate into N1 triacylglycerols in vitro (in the presence of ATP, CoA, and MgCl2) was increased threefold. The same large increase could not be achieved using citrate or EDTA in the presence of CMP or using AMP, UMP, or TMP in the presence of EGTA. The increased labelling of N1 triacylglycerols could be greatly reduced when CDP-choline was added to incubations containing EGTA and CMP. Levels of endogenous N1 diacylglycerols increased threefold following a 10-min incubation in the presence of buffer (pH 7.4) and MgCl2, when CMP and EGTA were also added. Of the major N1 phospholipids, phosphatidylcholine was most similar in fatty acid composition to the enlarged endogenous diacylglycerol pool. The rate of formation of oleoyl-CoA in fraction N1 was not significantly changed by the presence of EGTA and CMP. Rates of triacylglycerol labelling could only be modestly increased when EGTA and CMP were added to incubations containing N1 samples with artificially enlarged endogenous diacylglycerol pools (produced by phospholipase C preincubations). It is suggested that EGTA, as a Ca2+ chelator, and CMP, as a substrate, may allow an enhanced diacylglycerol production mediated by the back reaction of cholinephosphotransferase in N1. The endogenous N1 diacylglycerol produced in the absence of EGTA and CMP may come from another metabolic route.

Animals↗

Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Johns Hopkins study.

The Johns Hopkins Lung Project was designed to determine whether the addition of cytologic screening to the radiographic screening of high-risk volunteers could enhance the early detection of asymptomatic lung cancer and whether early therapeutic intervention in detected cases could significantly reduce the mortality from this disease. Male volunteers, 45 yr of age and older, who smoked at least 1 pack of cigarettes per day were recruited from the Baltimore metropolitan area. All of the 10,387 acceptable high-risk volunteers received annual chest radiographic screening. By random assignment, one half received cytologic examination of induced sputum in addition to the roentgenogram. This report describes the results of the initial screening. Compared with usual methods of clinical diagnosis, screening by both roentgenography and cytology identified a greater proportion of the lung cancer cases at an earlier stage. Screening by sputum cytology was found to improve the detection only of squamous cell carcinoma. In the dual-screen group, sputum cytology accounted for 28% of the detected cases, and resulted in 39% additional detection of lung cancer over that achieved by roentgenography. There was no corresponding decrease in prevalence. Lung cancers detected by cytology alone were found at very early stages. Although there has been an increase in average survival, much of this increase, if not all, may have resulted from lead-time and sampling bias.

Adenocarcinoma↗

Staging of bronchial carcinoma.

Survival curves for 173 patients with pathologic Stage I and II bronchial carcinoma were calculated. These curves demonstrated far too much heterogeneity in patients with pathologic Stage I disease. We recommend that the American Joint Committee Staging System be modified so that patients with T1N0 tumors are classified as Stage I disease and patients with T1N1 , T1N0 and T2N1 tumors are classified as Stage II disease.

Bronchial Neoplasms↗

Prognostic factors in patients with stage I, estrogen receptor-negative carcinoma of the breast. A clinicopathologic study.

In order to aid in the identification of a group of breast cancer patients at high risk of recurrence in whom the possible value of adjuvant chemotherapy might be most readily demonstrable, the authors reviewed the clinicopathologic features of 74 women with infiltrating, Stage I, estrogen receptor-negative breast carcinoma. They found significant correlations between short-term recurrence (within 2 years) and extensive necrosis (P less than 0.005), anaplastic tumor nuclear morphology (P less than 0.01), a positive family history of breast carcinoma (P less than 0.05), diffuse hyperplasia of axillary lymph nodes (P less than 0.05), and young age (P less than 0.05). Twenty percent of all patients experienced recurrence within 2 years, while recurrence was noted in 32% of patients with highly pleomorphic nuclei, 38% of those with extensive necrosis, and 45% of those with a positive family history. Recurrence was noted in 55% of the small number of patients with both anaplastic nuclear morphology and a positive family history. These apparent risk factors for early recurrence may be helpful in prospectively selecting patients most eligible to receive adjuvant chemotherapy.

Adult↗

The rapid incorporation of radioactive fatty acid into triacylglycerols during the in vitro acylation of native lipids of neuronal nuclei.

Using neuronal nuclei (N1) and microsomes (P3) isolated from cerebral cortices of 15-day-old rabbits, the incorporation of [14C]oleate was followed in vitro, making use of fatty acid activation factors and endogenous membrane acyl acceptors. Of the lipids of N1, it was triacylglycerol which showed the highest rates of labelling and which represented 71-80% of the total incorporated radioactivity in this fraction. Specific rates of N1 triacylglycerol formation were 63-166 times those of P3 triacylglycerols (based upon membrane phospholipid content). In P3, phospholipids made up 85% of the total microsomal lipid labelling. The incorporation of oleate was dependent upon ATP and coenzyme A, and acyl-CoA synthetase activities were demonstrated in N1 and P3 (specific activity ratio, N1:P3 = 4.5). Using exogenous [14C]oleoyl-CoA, high rates of N1 triacylglycerol labelling were still seen relative to P3, but rates of diacylglycerol and phospholipid labelling were substantially elevated in both fractions in contrast to rates found using [14C]oleate. By increasing levels of endogenous diacylglycerol using preincubations with phospholipase C, a 3-fold increase was seen in specific rates of triacylglycerol formation in both fractions in subsequent assays with [14C]oleate. A 4.5-fold increase in N1 diacylglycerol concentrations was found when N1 was incubated for 10 min in the absence of fatty acid, ATP and coenzyme A. It is concluded that neuronal nuclei have a very active diacylglycerol acyltransferase as well as the ability to generate diacylglycerol substrates.

Acylation↗

Concurrent radiochemotherapy in advanced breast cancer.

An initial trial to determine whether the theoretical advantage of concurrent systemic chemotherapeutic protection and local control (by radiation) could be achieved has been applied to 16 patients with breast cancer (Stage 3 and 4). CMFP/CMF combination chemotherapy has been administered with external irradiation (5000 rad breast, 4000-4400 rad nodes). External irradiation was successfully accomplished with tangenital fields to avoid combined modality esophagitis while achieving internal mammary node irradiation. Six patients subsequently received Iridium-192 interstitial implantation. Six patients treated preoperatively (4000 rad, breast) were able to have modified mastectomy within 3-6 weeks of completing radiation therapy without graft requirement or undue morbidity. Acute reactions during therapy included some amplification of epidermitis and myelosuppression. Prolongation of the radiation treatment course occurred in two patients and delay in chemotherapy cycles in four patients. In two patients, the leukocyte count nadir was below 1000 and one was hospitalized with fever. The majority of the patients achieved 75% of the designed chemotherapeutic doses in the ensuing year. Many of the patients with advanced disease were administered an Adriamycin-containing regimen upon completion of the radiation therapy. The current results suggest that it would be feasible to initiate a randomized prospective study using these techniques to compare sequential and concomitant chemo-radiation therapy in primary breast cancer to determine whether there is significant advantage in local control and duration of NED survival in either of the treatment regimens.

Adult↗

Magnetic bones in human sinuses.

Studies on the interaction of magnetic fields and biological organisms have centred on the influence of applied magnetic fields on the physiology and behaviour of organisms, including humans, and a search for magnetic sources within the organisms themselves. Evidence continues to accumulate that a wide range of organisms, from bacteria to vertebrates, can detect and orient to ambient magnetic fields (for examples see refs 2-4). Since the discovery that magnetic orientation by bacteria was due to the presence within the organism of magnetic particles of the ferric/ferrous oxide, magnetite, the search has begun for other biogenic deposits of inorganic magnetic material and ways in which the possession of such material might confer on the organism the ability to orient to ambient magnetic fields. Such magnetic material, often identified as magnetite, has been discovered in bees, homing pigeons, dolphins and various other organisms, including man. A variety of hypotheses for the use of magnetite in magnetic field detection have been proposed. We report here that bones from the region of the sphenoid/ethmoid sinus complex of humans are magnetic and contain deposits of ferric iron. The possible derivations and functions of these deposits are discussed.

Bone and Bones↗

A comparison of the rates of incorporation of fatty acids during the rapid synthesis in vitro of endogenous triacylglycerols by neuronal nuclei.

The incorporation of radioactive palmitate, oleate, linoleate, and arachidonate into endogenous triacylglycerols was followed in vitro using neuronal nuclei (N1) isolated from cerebral cortices of 15-day-old rabbits. Specific rates of incorporation of fatty acids into N1 triacylglycerols were 33-42 times and more than 100 times the corresponding values for cerebral cortex homogenates and microsomal fractions (P3), respectively. Acyl-CoA synthetase specific activities in N1 were 2.2 to 3.2 times the specific rates for fatty acid incorporation into N1 triacylglycerols. Using single fatty acids, N1 acyl-CoA synthetase showed a preference for linoleate which was more highly marked in linoleate-palmitate and linoleate-arachidonate competitions. In fatty acid incorporation into N1 triacylglycerols a preference for linoleate in competition with palmitate was noted; however, there was also a relatively higher utilization of arachidonate shown competitively than was noted in acyl-CoA synthesis. The data suggested that N1 diacylglycerol acyl transferase shows a selectivity for arachidonoyl-CoA in comparison with CoA esters of palmitate or oleate. Molecular class analyses of radioactive triacylglycerol products indicated that native endogenous N1 diacylglycerols bearing arachidonate or fatty acids of equal or higher unsaturation were used preferentially in N1 triacylglycerol synthesis. This preference was significantly decreased when higher levels of endogenous diacylglycerols were produced in N1 following a phospholipase C preincubation.

Animals↗

Achalasia of the cardia associated with pulmonary sarcoidosis.

The case of a patient with sarcoidosis and symptoms suggestive of achalasia cardia is presented. Because of increasingly severe dysphagia, cardiomyotomy was performed and biopsy specimens of the esophageal wall were obtained. Light and electron microscopy revealed lesions of the nerves in Auerbach's plexus consisting of an inflammatory process and demyelinization of the nerve fibers. Since the operation, the patient has been swallowing without difficulty. Although previous reports have described dysphagia in patients with sarcoidosis, presumably secondary to mechanical compression by adjacent lymph nodes or infiltration of the esophageal wall by sarcoid granulomata, this report documents for the first time that dysphagia can also be caused by direct involvement of the innervation of the esophagus by sarcoidosis.

Deglutition Disorders↗

Cholinephosphotransferase activities in microsomes and neuronal nuclei isolated from immature rabbit cerebral cortex: the use of endogenously generated diacylglycerols as substrate.

A neuronal nuclear fraction (N1) and a microsomal fraction (P3) were isolated from homogenates of cerebral cortices of 15-day-old rabbits. A nuclear envelope fraction (E) was prepared from N1. To assay cholinephosphotransferase, diacylglycerols were first generated in the membranes of these subfractions using a phospholipase C (Bacillus cereus) preincubation. With levels of endogenous diacylglycerols producing maximal specific cholinephosphotransferase activities, an activity ratio of 1:1:5 was found for N1, P3, and E, respectively. An independent neuronal nuclear cholinephosphotransferase, concentrated in nuclear membranes, is indicated. With regard to changes in pH and concentrations of MgCl2 and CDP-choline, N1 and P3 activities responded in a similar manner. However, in contrast to P3, N1 activities we much more profoundly inhibited at low levels of Triton X-100 (0.01-0.02 w/v%) and N1 showed quite significant levels of cholinephosphotransferase activity in the absence of a phospholipase C preincubation. Choline phosphotransferase in N1 and P3 showed Km values for CDP-choline (0.028 and 0.031 mM, respectively) which were much lower than corresponding literature values determined using exogenous diacylglycerols as substrates for this enzyme. The presence of cholinephosphotransferase in neuronal nuclear membranes reflects a rather exceptional nuclear autonomy. This may be related to a need to maintain nuclear phospholipid in the absence of a well-developed endoplasmic reticulum at early stages of neuronal development or to synthesize phospholipid in response to functions unique to the nucleus.

Animals↗