Showing papers by "Oregon Health & Science University published in 1986"
TL;DR: It is suggested that dietary omega 3 fatty acids are retina and brain, and abnormally low levels of 22:6 omega 3 may produce alterations in the biophysical properties of photoreceptor and neural membranes that may underlie these functional impairments.
Abstract: Docosahexaenoic acid [22:6 omega 3; 22:6-(4,7,10,13,16,19)] is the major polyunsaturated fatty acid in the photoreceptor membranes of the retina and in cerebral gray matter. It must be obtained either from the diet or by synthesis from other omega 3 fatty acids, chiefly alpha-linolenic acid (18:3 omega 3). We tested the effect of dietary omega 3 fatty acid deprivation during gestation and postnatal development upon the fatty acid composition of the retina and cerebral cortex and upon visual function. Rhesus monkeys (Macaca mulatta) were fed semipurified diets very low in 18:3 omega 3 throughout pregnancy, and their infants received a similar diet from birth. A control group of females and their infants received a semipurified diet supplying ample 18:3 omega 3. In near-term fetuses and newborn infants of the deficient group, the 22:6 omega 3 content of phosphatidylethanolamine was one-half of control values in the retina and one-fourth in cerebral cortex. By 22 months of age, the content of 22:6 omega 3 in these tissues approximately doubled in control monkeys, but it failed to increase in the deficient group. Low levels of 22:6 omega 3 in the deficient animals' tissues were accompanied by a compensatory increase in longer-chain omega 6 fatty acids, particularly 22:5 omega 6. Functionally, the deficient animals had subnormal visual acuity at 4-12 weeks of age and prolonged recovery time of the dark-adapted electroretinogram after a saturating flash. Abnormally low levels of 22:6 omega 3 may produce alterations in the biophysical properties of photoreceptor and neural membranes that may underlie these functional impairments. The results of this study suggest that dietary omega 3 fatty acids are retina and brain.
902 citations
Journal Article•
TL;DR: The excitement and attention focused on cellular oncogenes in recent years is now turning toward growth factors, not only as they concern the control of normal cell growth but also the involvement of growth factor-initiated pathways in the etiology of cancer.
Abstract: Growth factors, defined as polypeptides that stimulate cell proliferation, are major growth-regulatory molecules for cells in culture and probably also for cells in vivo. Nontransformed cells show an absolute requirement for growth factors for proliferation in culture and generally more than one growth factor is required. Under usual culture conditions, growth factors are more rapidly depleted than other media components and thus become rate limiting for proliferation. The loss of or decreased requirement for specific growth factors is a common occurrence in neoplastically transformed cells and may lead to a growth advantage, a cardinal feature of cancer cells. Recent work with transforming growth factors, the platelet-derived growth factor, and oncogenes has produced some insight into the mechanisms through which alterations in growth factor-receptor-response pathways could lead to a growth advantage. Evidence has been derived for autocrine secretion in which the cell produces its own growth factor. Many transformed mesenchymal cells produce PDGF (the product of the c-sis proto-oncogene) and certain transformed cells both produce and respond in a growth-stimulatory manner to TGF beta. With TGF beta, which is a growth inhibitor for certain epithelial and other cell types, the loss of the normal inhibitory response in transformed cells could have the same result as the activation of a growth-stimulatory response. Two proto-oncogenes, erbB and fms, encode growth factor receptors. In the erbB case, the viral erbB aberrant receptor produced is truncated and appears to be constitutively activated without the need for a growth factor. Recent studies suggest that the p21 product of the ras oncogene may be an obligatory intermediate in transducing the growth factor signal. Activation of ras may, therefore, activate the growth factor pathway without the need for either a growth factor or its receptor. The transcription of myc and fos is induced by growth factor stimulation of quiescent cells. The protein products of both are nuclear associated and conceivably could be involved in regulating other genes important in the control of cell proliferation. Activation or inappropriate expression of either myc or fos could produce the same end result as stimulation of a growth factor pathway leading to a growth advantage. Study of the molecular mechanism(s) of growth factor action has just begun. The excitement and attention focused on cellular oncogenes in recent years is now turning toward growth factors, not only as they concern the control of normal cell growth but also the involvement of growth factor-initiated pathways in the etiology of cancer.(ABSTRACT TRUNCATED AT 400 WORDS)
868 citations
TL;DR: The construction and characterization of a murine monoclonal antibody specific for type VII collagen is reported, which demonstrates metal deposition upon anchoring fibrils at both ends of these structures, as predicted by the location of the epitope ontype VII collagen.
Abstract: Anchoring fibrils are specialized fibrous structures found in the subbasal lamina underlying epithelia of several external tissues. Based upon their sensitivity to collagenase and the similarity in banding pattern to artificially created segment-long spacing crystallites (SLS) of collagens, several authors have suggested that anchoring fibrils are lateral aggregates of collagenous macromolecules. We recently reported the similarity in length and banding pattern of anchoring fibrils to type VII collagen SLS crystallites. We now report the construction and characterization of a murine monoclonal antibody specific for type VII collagen. The epitope identified by this antibody has been mapped to the carboxyl terminus of the major helical domain of this molecule. The presence of type VII collagen as detected by indirect immunofluorescence in a variety of tissues corresponds exactly with ultrastructural observations of anchoring fibrils. Ultrastructural immunolocalization of type VII collagen using a 5-nm colloidal gold-conjugated second antibody demonstrates metal deposition upon anchoring fibrils at both ends of these structures, as predicted by the location of the epitope on type VII collagen. Type VII collagen is synthesized by primary cultures of amniotic epithelial cells. It is also produced by KB cells (an epidermoid carcinoma cell line) and WISH (a transformed amniotic cell line).
543 citations
TL;DR: This report, which uses standardized interviews by psychiatrists, describes the psychiatric effects on 40 Cambodian high school students in the United States who suffered massive trauma from 1975 to 1979.
Abstract: This report, which uses standardized interviews by psychiatrists, describes the psychiatric effects on 40 Cambodian high school students in the United States who suffered massive trauma from 1975 to 1979. They endured separation from family, forced labor and starvation, and witnessed many deaths because of the Pol Pot regime. After 2 years of living in refugee camps, they immigrated to the United States at about age 14. Four years after leaving Cambodia, 20 (50%) developed posttraumatic stress disorder; mild, but prolonged depressive symptoms were also common. Psychiatric effects were more common and more severe when the students did not reside with a family member.
483 citations
TL;DR: Neuropsychological, neurophysiological, and neuropathological evidence that brain damage can occur in the absence of gross neurological deficits after mild injuries is reviewed.
Abstract: Seemingly mild head injuries frequently result in persisting postconcussive syndromes. The etiology of these symptoms is often controversial. Neuropsychological, neurophysiological, and neuropathological evidence that brain damage can occur in the absence of gross neurological deficits after mild injuries is reviewed. Direct impact to the head is not required to cause brain injury. Understandably, psychological factors also play a role in post-head-injury disability, but the effect of compensation claims and preinjury psychopathology is often secondary to organic factors. Persons over age 40 or with a history of previous head injury are more vulnerable to protracted symptomatology.
466 citations
TL;DR: It is suggested that primary particulate carbon emissions were the principal contributor to long-term average fine aerosol carbon concentrations in the Los Angeles area during 1982.
Abstract: A fine particle air monitoring network was operated in the Los Angeles area during 1982. It was found that carbonaceous aerosols accounted for typically 40% of total fine particle mass loadings at most monitoring sites. The ratio of total carbon (TC) to elemental carbon (EC) in ambient samples and in primary source emissions was examined as an indicator of the extent of secondary organic aerosol formation. It was found that TC to EC ratios at all
sites on average are no higher than recent estimates of the TC to EC ratio in primary source emissions. There is little evidence of the sustained summer peak in the ratio of TC to EC that one might expect if greatly enhanced secondary organics production occurs during the photochemical smog season. The TC to EC ratio does rise by the time that air masses reach the prevailing downwind edge of the air basin as would be expected if secondary organics are being formed during air parcel transport, but the extent of that increase is modest. These results suggest that primary particulate carbon emissions were the principal contributor to long-term average fine aerosol carbon concentrations in the Los Angeles area during 1982.
414 citations
TL;DR: Melatonin production clearly declined with age but was not influenced by other demographic variables or by season of the year.
Abstract: The purpose of this study was to investigate the effects of time of year and demographic variables on the amplitude of melatonin production in normal human subjects. Melatonin production was estimated by measuring the overnight excretion of its major urinary metabolite, 6-hydroxymelatonin. Urine was collected on three consecutive nights in the summer from a sample of 60 normal subjects balanced for sex and age. The collections were repeated in a subgroup during the winter. Melatonin production clearly declined with age but was not influenced by other demographic variables or by season of the year.
393 citations
TL;DR: A new and distinct syndrome involving an interstitial deletion of short arm of chromosome 17 in nine unrelated patients ranging in age from 3 months to 65 years is described.
Abstract: We describe a new and distinct syndrome involving an interstitial deletion of the short arm of choromosome 17 in nine unrelated patients (six males; three females) ranging in age from 3 months to 65 years. In eight patients, a deletion of a portion of band 17p11.2 was associated with a striking similar phenotype including brachycephaly, midface hypoplasia, prognathism, hoarse voice, and speech delay with or without hearing loss, psychomotor and growth retardation, and behavior problems. The one patient with a complete deletion of band 17p11.2 was more severely affected with facial malformations, cleft palate, and major anomalies of cardiac, skeletal, and genitourinary systems; the patient died at age 6 months. Careful cytogenetic analysis including high-resolution techniques will be important for the further identification of patients with this previously unrecognized deletion syndrome.
350 citations
TL;DR: The isolation and sequencing of a cDNA encoding bovine chromogranin A is reported, providing the first complete primary structure of a chromog Granin protein, and the presence of chromoganin mRNA in the parathyroid indicates that chromogramin A and SP-I are identical.
Abstract: Chromogranin A is contained in storage vesicles of chromaffin cells of the adrenal medulla and released with catecholamines when the splanchnic nerve is stimulated1,2. Chromogranin A is similar to secretory protein I (SP-I), a major secreted protein of the parathyroid3. Chromogranin A/SP-I immunoreactivity is abundant in endocrine cells that secrete peptide hormones from storage vesicles4–7. Chromogranins may act in neuroendocrine secretion by binding intravesicular calcium8,9. Serum levels of chromogranin are raised in hypertension10 and endocrine neoplasia8,10,11. We report here the isolation and sequencing of a cDNA encoding bovine chromogranin A, providing the first complete primary structure of a chromogranin protein. Chromogranin A is a highly acidic protein with an apparent relative molecular mass (Mr) of 75,000 on SDS-PAGE, but an actual Mr of 48,000. Adrenal medulla, brain, pituitary and parathyroid are all sites of synthesis of chromogranin A. The primary structure of chromogranin A, and the presence of chromogranin mRNA in the parathyroid, indicate that chromogranin A and SP-I are identical.
301 citations
TL;DR: A wide range of primary pharmacological actions of dimethyl sulfoxide (DMSO) has been documented in laboratory studies: membrane penetration, membrane transport, effects on connective tissue, anti-inflammation, nerve blockade (analgesia), bacteriostasis, diuresis, enhancement or reduction of the effectiveness of other drugs.
272 citations
01 Dec 1986
TL;DR: In this paper, the authors measured the amount of organic carbon adsorbed onto the back-up filter behind a Teflon front filter with both filter combinations sampling at the same face velocity.
Abstract: Abstract The concentration (μgC m−3) of aerosol organic carbon as determined by collection with quartz fiber filters was found to exhibit a significant decrease with increasing filter face velocity. A similar face velocity dependence was found for organic carbon on back-up quartz fiber filters behind either quartz fiber front filters (QQ combination) or Teflon membrane front filters (TQ combination). Additionally, the concentration of organic carbon on the back-up filter in the TQ combination was always greater than on the back-up filter in the QQ combination. The most likely explanation for these observations is the adsorption or organic vapors onto the filter medium itself. The amount of organic carbon adsorbed onto the quartz fiber front filter can be approximated by measuring the amount of organic carbon on a quartz fiber back-up filter behind a Teflon front filter with both filter combinations sampling at the same face velocity. Making the correction in such a manner removes most of the face velocity dependence inthe resultant concentrations. For 24 h sampling in Portland, Oregon, at a face velocity of 40 cm s−1, the correction exceeded 50% for uncorrected organic carbon concentrations of 2 μgC m−3 but decreased to 15% at 16 μgC m−3.
TL;DR: The coronary circulation of swine was studied to establish adequate baseline information for using swine in cardiovascular research and shows that the coronary anatomy but also the distribution of blood supply to particular areas or structures of the swine heart are very similar to that of humans.
Abstract: The coronary circulation of swine was studied to establish adequate baseline information for using swine in cardiovascular research. Of 65 hearts from domestic and miniature pigs, 45 were injected with a methacrylate plastic and prepared as coronary artery casts whose branches were described and measured, and 20 were injected with different coloured dyes in the right, left anterior descending, and circumflex coronary arteries so that horizontal sections of the heart showed the distribution of each artery and the source of blood supply to particular areas or structures of the heart. Like man, the swine had a left coronary artery that was larger in diameter and longer than the right coronary artery. The right coronary artery was almost always dominant (78%), supplying the posterior septum and atrioventricular node via the posterior descending coronary artery. Eight (17%) of the hearts possessed a balanced blood supply. Two (5%) hearts had a left dominant supply. The intracoronary artery dye injections showed that 72.4% of the right ventricular mass was supplied by the right coronary artery and 27.6% by the left anterior descending coronary artery. In the left ventricle 49% of the mass was supplied by the left anterior descending coronary artery, 25.5% by the right coronary artery, and 25.5% by the circumflex coronary artery. The left anterior descending coronary artery supplied 58% of the interventricular septal mass, while the posterior descending coronary artery supplied 42%. The distribution of the left anterior descending coronary artery branches to the ventricular wall varied inversely in number and size of its diagonal branches (2-9) with the obtuse marginal branches of the circumflex coronary artery which were occasionally more numerous or extended to the apex. The blood supply to the sinoatrial node was always by a branch of the right coronary artery. This analysis shows that not only the coronary anatomy but also the distribution of blood supply to particular areas or structures of the swine heart are very similar to that of humans.
TL;DR: Between September 1978 and December 1985, 450 case reports of serious respiratory and cardiovascular events and 32 cases of death attributed to ophthalmic timolol were received by the United States Food and Drug Administration and the National Registry of Drug-Induced Ocular Side Effects.
TL;DR: Monoclonal antibodies that react with hematopoietic cells and their precursors in a stage and lineage restricted fashion were used in indirect immunofluorescence assays to examine leukemic cells from 105 pediatric age patients and the usefulness of these antibodies in distinguishing leukemias of myeloid from those of lymphoid origin was demonstrated.
TL;DR: A general solution to the fundamental integral equation for ion binding in a multiligand system is given and a close examination of the continuous stability function model shows that it contains implicitly the same assumption as the affinity spectrum approach and thus leads also to discrete ligands.
Abstract: In this paper the authors examine critically the theory underlying discrete and continuous multiligand models for metal-humate binding. The concepts and equations that unify the various models are presented, and a general solution to the fundamental integral equation for ion binding in a multiligand system is given. Particular attention is paid to the continuous distribution models (normal distribution, affinity spectrum, and continuous stability function) which are relatively new tools in the field of metal-humate complexation. It is shown that the lower half and extreme right of the Gaussian ligand distribution assumed in the normal distribution model never affect metal speciation measurably and hence are not knowable. It is also shown that an affinity spectrum does not correspond to an actual distribution of ligands; rather, each peak in the spectrum indicates the most probable stability constant controlling metal binding in a particular region of the experimental formation function. Application of the affinity spectrum model leads to a set of discrete ligands. A close examination of the continuous stability function model shows that it contains implicitly the same assumption as the affinity spectrum approach and thus leads also to discrete ligands.
TL;DR: Restriction analysis of bovine genomic DNA suggests only one gene for CPE, consistent with a broad role for C PE in the biosynthesis of many neuropeptides.
Abstract: Carboxypeptidase E (enkephalin convertase) was first identified as the carboxypeptidase B-like enzyme involved in the biosynthesis of enkephalin in bovine adrenal chromaffin granules1. A similar enzyme is present in many brain regions1,2 and in purified secretory granules from rat pituitary3 and rat insulinoma4. Within the secretory granules, carboxypeptidase E (CPE) activity is found in both a soluble and a membrane-bound form1, which differ slightly in relative molecular mass (Mr)5. Here, to investigate whether the CPE activities in the various tissues are produced from a single gene, purified CPE was partially sequenced and oligonucleotide probes were used to isolate a clone encoding CPE from a bovine pituitary complementary DNA library. This cDNA hybridizes to bovine pituitary poly(A)+ RNAs of approximately 3.3, 2.6 and 2.1 kilobases (kb), with the 3.3-kb messenger RNA the predominant species. The predicted amino-acid sequence of the cDNA clone contains the partially determined sequences of CPE, several pairs of basic amino acids and displays some homology with both carboxypeptidases A and B. Restriction analysis of bovine genomic DNA suggests only one gene for CPE. This is consistent with a broad role for CPE in the biosynthesis of many neuropeptides.
TL;DR: It is indicated that 5 to 10 years after lower extremity DVT 80% of patients will have both symptoms and abnormal venous hemodynamics regardless of the initial site of the thrombosis.
TL;DR: The results justify considering endoscopic biliary prosthesis as the treatment of choice in nonresectable jaundiced patients with carcinoma of the head of the pancreas with pancreatic carcinoma for palliation of obstructive jaundice.
TL;DR: Results indicate that a decline in renal function and alterations in vitamin D metabolism occur with aging in normal men, and these changes contribute to, if not cause, the associated decline in skeletal mineral content in aging men.
Abstract: The effects of aging on calcium and bone metabolism have not been systematically examined in men. To identify age-related alterations in vitamin D and PTH physiology and to assess their impact on skeletal health, we studied 62 normal men, aged 30-92 yr. The men were in excellent health, and none had any evidence of metabolic bone disease and/or known risk factors for osteopenia. Serum 25-hydroxyvitamin D (25OHD) concentrations declined steadily with advancing age (r = -0.47; P less than 0.001), and there was a corresponding decline in serum 24,25-dihydroxyvitamin D [24,25-(OH)2D] levels (r = -0.41; P less than 0.001). Serum 1,25-(OH)2D concentrations, however, did not vary over this age range (r = -0.07; P = NS). Plasma PTH levels increased with aging (r = -0.24; P less than 0.001), and there was a concomitant increase in urinary cAMP excretion (r = 0.38; P less than 0.001). Renal function (creatinine clearance) clearly declined with increasing age (r = -0.71; P less than 0.001). In conjunction with these changes in calcium metabolism, radial and vertebral bone mineral content declined. Whereas the fall in radial bone mineral content (single photon absorptiometry) at both proximal and distal sites was slight, there was a marked decrease in vertebral bone mineral content, as measured by quantitative computed tomography (r = -0.72; P less than 0.0001). The fall in vertebral bone mineral content correlated well with the declines in serum 25OHD and 24,25-(OH)2D concentrations (r = 0.47; P less than 0.001 and r = 0.51; P less than 0.001, respectively) and with the decline in renal function (r = 0.46; P less than 0.001). Multiple regression analysis revealed that the effects of aging on bone mineral content could be accounted for in large part by concomitant changes in mineral metabolism. Both the decline in renal function and the fall in serum 24,25-(OH)2D levels were closely associated with the fall in bone mineral content. These results indicate that a decline in renal function and alterations in vitamin D metabolism occur with aging in normal men. These changes contribute to, if not cause, the associated decline in skeletal mineral content in aging men.
TL;DR: These studies indicate that chemotherapeutic drug delivery to tumors (as well as surrounding brain) can be augmented by osmotic BBB modification and that such therapy can result in a prolongation of survival.
Abstract: Reversible osmotic blood-brain barrier (BBB) modification was used in 38 patients with glioblastoma to enhance the delivery of chemotherapeutic agents. The patients ranged in age from 14 to 70 years (mean, 43), and all had prior surgery and radiation; 5 had also received systemic chemotherapy. Karnofsky Performance Status (KPS) scores ranged from 60 to 100% (mean, 79) on admission to the treatment program. Barrier modification was achieved by intracarotid or intravertebral artery infusion of mannitol, and a chemotherapy regimen of methotrexate, cytoxan, and procarbazine was given in conjunction with barrier modification. The 38 glioblastoma patients were compared to two control groups of patients with glioblastoma; these encompassed 14 patients treated with surgery and radiation and 8 treated with surgery, radiation, and systemic chemotherapy. Survival analysis using the Cox Proportional Hazards Regression Model (corrected for age, sex, presence or absence of necrosis, and functional status) showed that patients receiving chemotherapy with BBB modification had a statistically significant (P = 0.0006) longer expected survival (17.5 months) than the control groups (12.8 and 11.4 months, respectively). Presently 16 patients of the barrier-enhanced treatment group are alive at 5 to 42 months from diagnosis (median, 20) with KPS scores ranging from 40 to 90% (median, 65). The neurological complications seen included a stroke-like syndrome in 3 patients (1 with decreased motor movement in the hand, 1 with marked hemiparesis, and 1 with hemiplegia), transient exacerbation of preexisting neurological deficits lasting 2 to 3 days, and a 15% incidence of seizures during or within 24 hours of the BBB modification. In 2 of the 38 patients, radiographic documentation of central nervous system tumor regression concurrent with the development of new tumor nodule(s) in portions of the brain distant from the region of osmotic BBB opening was seen. These studies indicate that chemotherapeutic drug delivery to tumors (as well as surrounding brain) can be augmented by osmotic BBB modification and that such therapy can result in a prolongation of survival.
TL;DR: A new method of precut papillotomy with a fine wire needle knife is presented, which involves the creation of an artificial choledochoduodenal fistula proximal to the papilla itself by making a 1to 1.5-cm long incision in the bulging intraduodental common duct.
TL;DR: This work demonstrates how DNA sequence dosage analysis can be used to study genetic disorders that are not readily amenable to standard cytogenetic analysis.
Abstract: Most individuals with cat eye syndrome (CES) have a supernumerary bisatellited chromosome which, on the basis of cytogenetic evidence, has been reported to originate from either chromosome 13 or 22. To resolve this question, a single-copy DNA probe, D22S9, was isolated and localized to 22q11 by in situ hybridization to metaphase chromosomes. The number of copies of this sequence was determined in CES patients by means of Southern blots and densitometry analysis of autoradiographs. In patients with the supernumerary chromosome, four copies were found, whereas in one patient with a duplication of part of chromosome 22, there were three copies. Therefore, the syndrome results from the presence of either three or four copies of DNA sequences from 22q11; there is no evidence that sequences from other chromosomes are involved. This work demonstrates how DNA sequence dosage analysis can be used to study genetic disorders that are not readily amenable to standard cytogenetic analysis.
TL;DR: Of 21 eyes in 18 patients treated in this manner, three eyes required retreatment of adjacent areas; otherwise, there were no recurrences in follow-up periods ranging from 5 months to 12 years.
TL;DR: In this paper, the authors found that peptides derived from pro-dynorphin and pro-vasopressin precursors coexist within neurosecretory vesicles of magnocellular neurons in the rat hypothalamus projecting to the posterior pituitary.
Abstract: Peptides derived from pro-dynorphin and pro-vasopressin precursors coexist within neurosecretory vesicles of magnocellular neurons in the rat hypothalamus projecting to the posterior pituitary. The secretory activity of these neurons can be stimulated using physiological manipulations known to increase plasma vasopressin levels, such as dehydration and salt-loading. With chronic osmotic challenge, the mRNAs for both pro-dynorphin and pro-vasopressin increase in parallel in the supraoptic and paraventricular nuclei of the hypothalamus, but not within the nonmagnocellular suprachiasmatic nucleus cell groups projecting elsewhere than the neural lobe. The results indicate an example of coordinate regulation of mRNA expression for coexisting peptides within the brain.
TL;DR: In school, students receiving a psychiatric diagnosis were more likely to be rated by their classroom teachers as withdrawn or daydreaming than as disruptive, and the crucial role of the school as a cultural agent of change became strongly evident.
Abstract: Forty Cambodian high school students who survived 4 years under the Pol Pot regime (1975–1979) and 6 Cambodian students who escaped their homeland prior to Pol Pot were studied by means of home interviews and school teacher ratings. In these findings, compared to psychiatric interview data on the same subjects, students reported more distress with school grades, peers and themselves than was observed by their caretakers. Many of their family members exhibited similar posttraumatic stress and depressive symptoms. In school, students receiving a psychiatric diagnosis were more likely to be rated by their classroom teachers as withdrawn or daydreaming than as disruptive. The crucial role of the school as a cultural agent of change became strongly evident.
TL;DR: In this article, a CT-guided needle biopsy of deep parenchymal lesions contributed to the diagnosis of primary central nervous system (CNS) lymphoma, integrating the techniques of needle brain biopsy, immunohistochemical staining for monoclonal antibody and chemotherapeutic drug delivery in association with blood-brain barrier modification.
Abstract: Current experience with 12 patients studied prospectively suggests a new approach in the diagnosis and treatment of primary central nervous system (CNS) lymphoma, integrating the techniques of needle brain biopsy, immunohistochemical staining for monoclonal antibody and chemotherapeutic drug delivery in association with blood-brain barrier modification. Computed tomography (CT)-guided needle biopsy of deep parenchymal lesions contributed to the diagnosis in six patients. Immunohistochemical staining methods detected monoclonal immunoglobulins in those patients so tested. Following diagnosis, the patients have been treated with multi-agent chemotherapy in conjunction with osmotic blood-brain barrier modification (five without antecedent cranial irradiation) with an initial complete response rate by CT scan in nine patients, a median follow-up of 19 months from diagnosis, and a 1-year survival of 75%. This experience emphasizes the value of CT-guided stereotaxic or CT-guided needle biopsy, which limits the need for therapy without a diagnosis or the need for a major craniotomy in what are commonly deep, paraventricular lesions. Immunoperoxidase cytochemical stains can detect monoclonal immunoglobulin characteristic of CNS B-cell malignant lymphomas and provide an important diagnostic aid when only modest quantities of tissue or cells are obtained. Finally, chemotherapy administered in conjunction with osmotic blood-brain barrier modification results in a clinical response rate and survival that are at least as effective as radiotherapy as a primary therapeutic modality.
TL;DR: The cholesterol/saturated-fat index (CSI) is a modification of a regression equation computed from metabolic studies designed to lower plasma lipids that indicates low saturated fat and cholesterol content and low atherogenicity.
TL;DR: Thirty-five consecutive patients with acute hematochezia, negative gastric aspirates, and negative sigmoidoscopy underwent urgent colonoscopy after Golytely purgation, suggesting that the procedure provides an opportunity for early nonoperative treatment of acute colonic hemorrhage.
Abstract: Thirty-five consecutive patients with acute hematochezia, negative gastric aspirates, and negative sigmoidoscopy underwent urgent colonoscopy after Golytely purgation. Mucosal visualization was excellent. Colonic bleeding lesions were identified in 24 of 35 patients, and hemorrhage originating proximal to the ileoceal valve was documented in three of these 35 patients. Therapeutic endoscopic electrocautery, employed in 12 of 35 patients, was effective in 11. The peroral preparation was well tolerated, and there were no complications of the preparation or of colonoscopy. The data suggest that urgent colonoscopy following Golytely purgation is a safe, sensitive, and specific diagnostic procedure that provides an opportunity for early nonoperative treatment of acute colonic hemorrhage.
TL;DR: Monitoring muscle bioenergetics with 31P‐NMR is valuable in documenting therapeutic improvements in mitochondrial myopathies and identifying differential therapeutic effects of vitamin K3 at rest and during exercise recovery.
Abstract: A patient with mitochondrial myopathy due to complex III deficiency who was treated with vitamin K3 (menadiol sodium diphosphate, 40 mg daily) and vitamin C showed clinical improvement. A 1-year study with phosphorus 31 nuclear magnetic resonance (31P-NMR) monitoring has shown that clinical and metabolic improvement was maintained by this therapy; increasing the dose of vitamin K3 to 80 mg daily improved the bioenergetic state of the patient's muscles at rest; postexercise recovery was less responsive to the increased dose; and a higher dose of vitamin K3 (80 mg/day) did not produce side effects. The differential therapeutic effects of vitamin K3 at rest and during exercise recovery are probably due to the differential kinetics of each metabolic state. Monitoring muscle bioenergetics with 31P-NMR is valuable in documenting therapeutic improvements in mitochondrial myopathies.
TL;DR: The in vitro binding of a synthetic androgen, methyltrienolone ([3H]-R1881), to brain and pituitary (PIT) cytosol and nuclear extracts was determined and the existence of specific receptors for androgen in male and female brain and PIT is confirmed, suggesting an important role for androgens in the control of PIT hormone secretion in the female.
Abstract: The in vitro binding of a synthetic androgen, methyltrienolone ([3H]-R1881), to brain and pituitary (PIT) cytosol and nuclear extracts was determined in male and female rats. Purified cytosol was prepared from PIT or hypothalamic-preoptic area-amygdala (HPA) and incubated in the presence of 0.1 to 10 nM [3H]-R1881. Scatchard analysis revealed the presence of a single, saturable, high-affinity binding site in PIT cytosol with a dissociation constant (Kd) of 0.42 X 10(-10) M in females and 0.95 X 10(-10) M in intact males. The Kd of HPA cytosol was much less in castrated males [0.47 +/- 0.05 (SEM) X 10(-10)M, n = 7] and females (0.63 +/- 0.1 X 10(-10) M, n = 4) than in intact males (5.8 +/- 1.1 X 10(-10) M, n = 8). Treatment of castrated males with dihydrotestosterone (DHT) for 24 h (250 micrograms/100 g of body weight) increased the Kd of HPA cytosol only slightly (1.6 X 10(-10) M, mean of two replicates). Scatchard analysis of salt-extracted nuclear androgen receptor (ARn) showed a single, high-affinity binding site with similar Kd values in PIT and HPA of intact and castrated, DHT-treated male rats (PIT Kd = 7.3 X 10(-10) M, 9.3 X 10(-10) M; HPA Kd = 1.5 X 10(-9) M, 1.3 X 10(-9) M, respectively). Competition studies involving a range of several radioinert steroids revealed that the binding of [3H]-R1881 to cytosol (ARc) and nuclear extract was specific for androgen receptor when triamcinolone acetonide (10 microM) was added. The ARc and ARn levels were quantified in PIT, preoptic area (POA), hypothalamus (HT), amygdala, hippocampus, and cortex by single point estimation. Significantly (p less than 0.01) greater amounts of ARc were detected in PIT of ovariectomized females (32.7 +/- 2.9 fmol/mg of protein) than in that of orchidectomized males (22.33 +/- 1.6 fmol/mg of protein). The highest levels in the brain were seen in HT and POA. Pituitary ARc in females varied throughout the estrous cycle. Significantly (p less than 0.01) greater amounts were detected on estrus (45.8 +/- 2.2 fmol/mg of protein) and proestrus (39.0 +/- 1.9 fmol/mg of protein) than on diestrus (29.2 +/- 1.5 fmol/mg of protein). These data confirm the existence of specific receptors for androgen in male and female brain and PIT, and suggest an important role for androgen in the control of PIT hormone secretion in the female.