Showing papers by "Johns Hopkins University published in 1985"

Matrix Analysis

Abstract: Linear algebra and matrix theory are fundamental tools in mathematical and physical science, as well as fertile fields for research. This new edition of the acclaimed text presents results of both classic and recent matrix analyses using canonical forms as a unifying theme, and demonstrates their importance in a variety of applications. The authors have thoroughly revised, updated, and expanded on the first edition. The book opens with an extended summary of useful concepts and facts and includes numerous new topics and features, such as: - New sections on the singular value and CS decompositions - New applications of the Jordan canonical form - A new section on the Weyr canonical form - Expanded treatments of inverse problems and of block matrices - A central role for the Von Neumann trace theorem - A new appendix with a modern list of canonical forms for a pair of Hermitian matrices and for a symmetric-skew symmetric pair - Expanded index with more than 3,500 entries for easy reference - More than 1,100 problems and exercises, many with hints, to reinforce understanding and develop auxiliary themes such as finite-dimensional quantum systems, the compound and adjugate matrices, and the Loewner ellipsoid - A new appendix provides a collection of problem-solving hints.

Analysis of Human Genetic Linkage

Abstract: The first and still the only book of its kind, this volume offers a concise introduction to human genetic linkage analysis and gene mapping. Jurg Ott provides mathematical and statistical foundations of linkage analysis for researchers and practitioners, as well as practical comments on available computer programs and websites. Each chapter ends with a set of problems, whose solutions are found at the end of the book. New to this edition is a chapter on complex traits, such as diabetes, some cancers, and psychiatric conditions. Also new is an overview of nonparametric approaches to linkage and association analysis. A chapter on two-locus inheritance introduces the reader to many of the intricate aspects of complex traits. Although the book's primary audience is in the field of genetics, physicians and others without sophisticated training in genetics can understand and apply the principles and techniques discussed.

The Hofmeister effect and the behaviour of water at interfaces.

Abstract: Starting from known properties of non-specific salt effects on the surface tension at an air–water interface, we propose the first general, detailed qualitative molecular mechanism for the origins of ion-specific (Hofmeister) effects on the surface potential difference at an air–water interface; this mechanism suggests a simple model for the behaviour of water at all interfaces (including water–solute interfaces), regardless of whether the non-aqueous component is neutral or charged, polar or non-polar Specifically, water near an isolated interface is conceptually divided into three layers, each layer being 1 water-molecule thick We propose that the solute determines the behaviour of the adjacent first interfacial water layer ( I 1 ); that the bulk solution determines the behaviour of the third interfacial water layer ( I 3 ), and that both I 1 and I 3 compete for hydrogen-bonding interactions with the intervening water layer ( I 2 ), which can be thought of as a transition layer The model requires that a polar kosmotrope (polar water-structure maker) interact with I 1 more strongly than would bulk water in its place; that a chaotrope (water-structure breaker) interact with I 1 somewhat less strongly than would bulk water in its place; and that a non-polar kosmotrope (non-polar water-structure maker) interact with I 1 much less strongly than would bulk water in its place We introduce two simple new postulates to describe the behaviour of I 1 water molecules in aqueous solution The first, the ‘relative competition’ postulate, states that an I 1 water molecule, in maximizing its free energy (—δG), will favour those of its highly directional polar (hydrogen-bonding) interactions with its immediate neighbours for which the maximum pairwise enthalpy of interaction (—δ H ) is greatest; that is, it will favour the strongest interactions We describe such behaviour as ‘compliant’, since an I 1 water molecule will continually adjust its position to maximize these strong interactions Its behaviour towards its remaining immediate neighbours, with whom it interacts relatively weakly (but still favourably), we describe as ‘recalcitrant’, since it will be unable to adjust its position to maximize simultaneously these interactions The second, the ‘charge transfer’ postulate, states that the strong polar kosmotrope–water interaction has at least a small amount of covalent character, resulting in significant transfer of charge from polar kosmotropes to water–especially of negative charge from Lewis bases (both neutral and anionic); and that the water-structuring effect of polar kosmotropes is caused not only by the tight binding (partial immobilization) of the immediately adjacent ( I 1 ) water molecules, but also by an attempt to distribute among several water molecules the charge transferred from the solute When extensive, cumulative charge transfer to solvent occurs, as with macromolecular polyphosphates, the solvation layer (the layer of solvent whose behaviour is determined by the solute) can become up to 5- or 6-water-molecules thick We then use the ‘relative competition’ postulate, which lends itself to simple diagramming, in conjunction with the ‘charge transfer’ postulate to provide a new, startlingly simple and direct qualitative explanation for the heat of dilution of neutral polar solutes and the temperature dependence of relative viscosity of neutral polar solutes in aqueous solution This explanation also requires the new and intriguing general conclusion that as the temperature of aqueous solutions is lowered towards o °C, solutes tend to acquire a non-uniform distribution in the solution, becoming increasingly likely to cluster 2 water molecules away from other solutes and surfaces (the driving force for this process being the conversion of transition layer water to bulk water) The implications of these conclusions for understanding the mechanism of action of general (gaseous) anaesthetics and other important interfacial phenomena are then addressed

Longitudinal Studies on the Rate of Decline in Renal Function with Age

Abstract: Serial creatinine clearances (5 to 14 studies) were obtained for 446 normal volunteers in the Baltimore Longitudinal Study of Aging followed between 1958 and 1981. When those subjects with possible renal or urinary tract disease and subjects on diuretics and antihypertensives were removed from the study, leaving a group of 254 "normal" subjects, the mean decrease in creatinine clearance was 0.75 ml/min/year. The slopes of the creatinine clearance vs. time fell into a normal (Gaussian) distribution around this mean. One third of all subjects followed had no absolute decrease in renal function (positive slope of creatinine clearance vs. time) and there was a small group of patients who showed a statistically significant increase (P less than 0.05) in creatinine clearance with age.

Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6 -tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity.

Abstract: N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces neuropathological and clinical abnormalities in humans, monkeys, and mice that closely resemble idiopathic parkinsonism. N-Methyl-4-phenylpyridine (MPP+), a metabolite of MPTP formed by monoamine oxidase B, is accumulated into striatal and cerebral cortical synaptosomes by the dopamine and norepinephrine uptake systems, respectively, whereas MPTP itself is not accumulated. The potencies of drugs in inhibiting [3H]MPP+ or [3H]dopamine uptake into striatal synaptosomes are very similar, as are potencies in inhibiting [3H]MPP+ or [3H]norepinephrine uptake into cortical synaptosomes. The Km values for [3H]MPP+ uptake are 170 and 65 nM and the Vmax values are 2 and 0.1 nmol/g of tissue per min in rat striatum and cortex, respectively, similar to values for [3H]dopamine uptake, Autoradiography of accumulated [3H]MPP+ in slices of rat brain shows high densities in the caudate-putamen and nucleus accumbens. Furthermore, blockade of dopamine uptake by mazindol prevents MPTP-induced damage to nigrostriatal dopamine neurons, indicating that MPP+ concentration into dopamine neurons explains their selective destruction by MPTP.

Congenital heart disease: prevalence at livebirth the baltimore-washington infant study

Abstract: The Baltimore-Washington Infant Study is a regional epidemiologic study of congenital heart disease. Among Infants born in the study area in 1981 and 1982, 664 had a diagnosis of congenital heart disease confirmed in the first year of life by echocardiography, cardiac catheterization, cardiac surgery, or autopsy. The prevalence rate was 3.7/1,000 livebirths for all cases and 2.4/1,000 livebirths for cases confirmed by invasive methods only. Diagnosis-specific prevalence rates of congenital heart disease are compared with those of eight previous case series. Changing diagnostic categorizations in the time span covered and methodological differences resulted in great variation of the data. However, the data of the New England Infant Cardiac Program which used the same case discovery methods showed similar occurrences of major morphologic abnormalities, suggesting that these are stable basic estimates in the eastern United States. For all case series, the rate of confirmed congenital heart disease was approximately 4/1,000 livebirths over the 40-year time span.

Hypomethylation of DNA from benign and malignant human colon neoplasms.

Abstract: The methylation state of DNA from human colon tissue displaying neoplastic growth was determined by means of restriction endonuclease analysis. When compared to DNA from adjacent normal tissue, DNA from both benign colon polyps and malignant carcinomas was substantially hypomethylated. With the use of probes for growth hormone, gamma-globin, alpha-chorionic gonadotropin, and gamma-crystallin, methylation changes were detected in all 23 neoplastic growths examined. Benign polyps were hypomethylated to a degree similar to that in malignant tissue. These results indicate that hypomethylation is a consistent biochemical characteristic of human colonic tumors and is an alteration in the DNA that precedes malignancy.

Spectral and statistical properties of the equilibrium range in wind-generated gravity waves

Abstract: Recent measurements of wave spectra and observations by remote sensing of the sea surface indicate that the author's (1958) conception of an upper-limit asymptote to the spectrum, independent of wind stress, is no longer tenable. The nature of the equilibrium range is reexamined, using the dynamical insights into wave–wave interactions, energy input from the wind and wave-breaking that have been developed since 1960. With the assumption that all three of these processes are important in the equilibrium range, the wavenumber spectrum is found to be of the form , where p ∼ ½ and the frequency spectrum is proportional to u*gσ−4. These forms have been found by Kitaigorodskii (1983) on a quite different dynamical basis; the latter is consistent with the form found empirically by Toba (1973) and later workers. Various derived spectra, such as those of the sea-surface slope and of an instantaneous line traverse of the surface, are also given, as well as directional frequency spectra and frequency spectra of slope.The theory also provides expressions for the spectral rates of action, energy and momentum loss from the equilibrium range by wave-breaking and for the spectrally integrated rates across the whole range. These indicate that, as a wave field develops with increasing fetch or duration, the momentum flux to the underlying water by wave-breaking increases asymptotically to a large fraction of the total wind stress and that the energy flux to turbulence in the water, occurring over a wide range of scales, increases logarithmically as the extent of the equilibrium range increases. Interrelationships are pointed out among different sets of measurements such as the various spectral levels, the directional distributions, the total mean-square slope and the ratio of downwind to crosswind mean-square slopes.Finally, some statistical characteristics of the breaking events are deduced, including the expected length of breaking fronts (per unit surface area) with speeds of advance between c and c+dc and the number of such breaking events passing a given point per unit time. These then lead to simple expressions for the density of whitecapping, those breaking events that produce bubbles and trails of foam, the total number of whitecaps passing a given point per unit time and, more tenuously, the whitecap coverage.

Topoisomerase II is a structural component of mitotic chromosome scaffolds

Abstract: We have obtained a polyclonal antibody that recognizes a major polypeptide component of chicken mitotic chromosome scaffolds. This polypeptide migrates in SDS PAGE with Mr 170,000. Indirect immunofluorescence and subcellular fractionation experiments confirm that it is present in both mitotic chromosomes and interphase nuclei. Two lines of evidence suggest that this protein is DNA topoisomerase II, an abundant nuclear enzyme that controls DNA topological states: anti-scaffold antibody inhibits the strand-passing activity of DNA topoisomerase II; and both anti-scaffold antibody and an independent antibody raised against purified bovine topoisomerase II recognize identical partial proteolysis fragments of the 170,000-mol-wt scaffold protein in immunoblots. Our results suggest that topoisomerase II may be an enzyme that is also a structural protein of interphase nuclei and mitotic chromosomes.

Inflammatory Mediators in Late Antigen-Induced Rhinitis

Abstract: To investigate the mechanisms responsible for the late-phase response in patients with allergies, we measured four biochemical mediators (histamine, tosyl-L-arginine methyl ester [TAME]—esterase, kinin, and prostaglandin D2) in nasal secretions after nasal challenge with pollen antigen in 12 patients with allergy. Nine patients had an immediate response and a recurrence of symptoms 3 to 11 hours after challenge. The clinical symptoms during recurrence were accompanied by a second increase in levels of histamine, TAME—esterase, and kinin over base-line values, although kinin levels were lower than during the immediate response. In contrast, although the levels of prostaglandin D2 were significantly increased during the immediate response, they did not increase above base line during the late response. Rechallenge with allergen 11 hours after the initial provocation, however, was associated with reappearance of all four biochemical mediators, including prostaglandin D2. We conclude that the late re...

Functional endoscopic sinus surgery. Theory and diagnostic evaluation.

Abstract: • The keys to functional endoscopic sinus surgery are an understanding of the underlying mechanisms of paranasal sinus disease and the ability to diagnose the causes accurately. Previously unrecognized causes of recurrent acute sinusitis and of chronic sinus symptomatology can now be identified by careful diagnostic evaluation. Systematic nasal endoscopy and high-resolution computed tomographic imaging provide complementary diagnostic information that can allow for the recognition of problems not identifiable by other means. The ability to diagnose these problems and to correct them with functional endoscopic surgery heralds new possibilities in the field. ( Arch Otolaryngol 1985;111:576-582)

Colocalization of neuropeptide Y immunoreactivity in brainstem catecholaminergic neurons that project to the paraventricular nucleus of the hypothalamus.

Abstract: Immunohistochemical methods were used in the rat to plot the distribution of neuropeptide Y (NPY) immunoreactivity in the paraventricular (PVH) and supraoptic (SO) nuclei of the hypothalamus, and a combined retrograde transport-double immunohistochemical labeling technique was used to determine the extent to which NPY immunoreactivity is coexpressed in brainstem cell groups that stain with antisera to phenylethanolamine-N-methyltransferase (PNMT; a marker for adrenergic neurons) or dopamine-s-hydroxylase (DBH; a marker for adrenergic and noradrenergic neurons) and also project to the PVH. The results confirm the existence of a major NPY-immunoreactive pathway that is in a position to influence each major class of output neurons in the PVH. Thus, most parts of the parvicellular division receive a dense input that is similar to, though somewhat more extensive than, the one stained by DBH antisera. However, in the magnocellular division catecholaminergic inputs are preferentially associated with vasopressinergic neurons, while NPY-stained fibers tend to be more evenly distributed in regions containing both oxytocinergic and vasopressingergic neurons, and their density appear to be lower than that of DBH-stained fibers. In the SO, only a moderate NPY-stained input was apparent, while, as described previously, DBH-immunoreactive fibers are rather dense and are preferentially distributed in vasopressinergic regions of the nucleus. The results of combined retrograde transport-double immunohistochemical labeling experiments may be summarized as follows: the vast majority of cells in the medulla that were retrogradely labeled after discrete implants of the fluorescent tracer true blue into the PVH, and were PNMT-immunoreactive, also stained for NPY. However, less extensive co-localization was detected in noradrenergic cell groups of the caudal medulla. About 60% of the retrogradely labeled-DBH positive cells in the Al cell group were also NPY-positive, while those in the caudal part of the nucleus of the solitary tract (the A2 cell group) usually failed to stain with anti-NPY. Similarly, in the locus coeruleus (the A6 cell group) where virtually all retrogradely labeled neurons were DBH-positive, only rarely were triply labeled cells detected. These results suggest that NPY immunoreactivity is extensively co-contained within adrenergic neurons of the C1, C2, and C3 groups that project to the PVH, while the correspondence in noradrenergic cell groups is less complete, and generally limited to a subset of neurons in the A1 cell group. Differences in the distribution of NPY- and DBH-stained inputs to the magnocellular division of the PVH and the SO suggest a complex arrangement of NPY-catecholamine colocalization in the A1 region. The staining patterns are consistent with the view that NPY is a neurotransmitter or neuromodulator of major importance in brainstem projections to the PVH and SO, and that by virtue of its distribution, NPY provides further differentiation of an elaborate system of ascending catecholaminergic inputs to the hypothalamus.

Sarcoidosis and its neurological manifestations.

Abstract: • Neurosarcoidosls is a disorder that is difficult to diagnose and manage. We assessed its neurological manifestations in 649 patients seen at The Johns Hopkins Hospital, Baltimore, from 1975 through 1980. Neurological problems could be attributed to neurosarcoidosis in 33 patients (5.1%). The presenting manifestation of sarcoidosis was neurological in 16 (48%) of them. Cranial neuropathy was the most frequent problem, and a peripheral facial nerve palsy was the single most common abnormality. Other manifestations were aseptic meningitis, hydrocephalus, parenchymatous disease of the central nervous system, peripheral neuropathy, and myopathy. Three-quarters of the patients were treated with steroids. The outcome was good in 27 (82%) of 33 episodes of neurological dysfunction in 25 patients with a well-documented clinical course. A thorough investigation of patients with suspected neurosarcoidosis is recommended to establish the diagnosis, delineate the extent of disease, and guide therapy.

Misleading postevent information and memory for events: arguments and evidence against memory impairment hypotheses.

Abstract: The claim that a person's memory for an event may be altered by information encountered after the event has been influential in shaping current conceptions of memory. The basis for the claim is a series of studies showing that subjects who are given false or misleading information about a previously witnessed event perform more poorly on tests of memory for the event than subjects who are not misled. In this article we argue that the available evidence does not imply that misleading postevent information impairs memory for the original event, because the procedure used in previous studies is inappropriate for assessing effects of misleading information on memory. We then introduce a more appropriate procedure and report six experiments using this procedure. We conclude from the results that misleading postevent information has no effect on memory for the original event. We then review several recent studies that seem to contradict this conclusion, showing that the studies do not pose problems for our position. Finally, we discuss the implications of our conclusions for broader issues concerning memory.

Primate globus pallidus and subthalamic nucleus: functional organization.

Abstract: Neuronal relations to active movements of individual body parts and neuronal responses to somatosensory stimulation were studied in the external (GPe) and internal (GPi) segments of the globus pallidus (GP) and the subthalamic nucleus (STN) of awake monkeys. In GPe (n = 249), GPi (n = 151), and STN (n = 153), 47, 29, and 28% of the cells, respectively, discharged in relation to active arm movements, 10, 11, and 15% to leg movements, and 22, 22, and 18% to orofacial movements. Of the neurons whose activity was related to arm movements, 26, 16, and 21% in GPe, GPi, and STN, respectively, discharged in relation to movements of distal parts of the limb. Of cells whose discharge was related to active limb movements, 37, 22, and 20% in GPe, GPi, and STN, respectively, also responded to passive joint rotation, which was usually specific in terms of joint and direction of movement. Only a small percentage of cells responded to muscle or joint palpation, tendon taps, or cutaneous stimulation. Short-latency, direction-specific neuronal responses to load perturbations confirmed the existence of proprioceptive driving. In both GPe and GPi, leg movement-related neurons were centrally located in the rostrocaudal and dorsoventral dimensions. In contrast, arm movement-related cells were found throughout the entire rostrocaudal extent of both segments, although in greater numbers caudally. In the central portions they were situated largely inferior and lateral to leg movement-related neurons. Neurons related to orofacial movements were largely confined to the caudal halves of both segments, where they were located largely ventral to arm movement-related cells. The STN cells whose activity was related to leg movements were observed largely in the central portions of the nucleus in the rostrocaudal and mediolateral dimensions. Cells whose activity was related to arm movements were found throughout the rostrocaudal extent of the nucleus, but were most numerous at the rostral and caudal poles. Neurons related to movements of the facial musculature and to licking and chewing movements were distributed over the entire rostrocaudal extent of the nucleus, where they generally occupied the ventrolateral regions. In all three nuclei, neurons with similar functional properties were sometimes clustered together. Within the arm and leg areas, however, there was no clear evidence for a simple organization of clusters related to different parts of the limb. These studies provide further evidence for a role of the basal ganglia in the control of limb movements.(ABSTRACT TRUNCATED AT 400 WORDS)

Hypertensive hypertrophic cardiomyopathy of the elderly.

Abstract: Using echocardiography, we identified 21 patients with a syndrome that included severe concentric cardiac hypertrophy, a small left ventricular cavity, and supernormal indexes of systolic function without concurrent medical illness or ischemic heart disease. Thirteen of the patients presented with dyspnea or chest pain. All patients studied had a history of hypertension and were compared with normotensive controls matched for age and sex. The patients were elderly (mean age, 73.3 years), predominantly female (16 patients), and mostly black (15 patients). Their cardiac function was characterized by excessive left ventricular emptying (ejection fraction on two-dimensional echocardiography [patients vs. controls], 79 +/- 4 vs. 59 +/- 5 per cent, P less than 0.001) and abnormal diastolic function as manifested by a prolonged early diastolic filling period (279 +/- 25 vs. 160 +/- 45 msec, P less than 0.001) and reduced peak diastolic dimension increase (11 +/- 4 vs. 16 +/- 5 cm per second, P less than 0.05). In spite of the clinical presentation of heart failure, all of 9 patients receiving either beta-receptor antagonists or calcium-channel blocking agents obtained symptomatic relief, whereas 6 of 12 patients receiving vasodilator medications had severe hypotensive reactions, including one death. We conclude that this unique subset of hypertensive patients has a clinical syndrome that warrants recognition and tailored management.

Comparison of the lay Diagnostic Interview Schedule and a standardized psychiatric diagnosis. Experience in eastern Baltimore.

Abstract: • We studied DSM-III diagnoses made by the lay Diagnostic Interview Schedule (DIS) method in relation to a standardized DSM-III diagnosis by psychiatrists in the two-stage Baltimore Epidemiologic Catchment Area mental morbidity survey. Generally, prevalence estimates based on the DIS one-month diagnoses were significantly different from those based on the psychiatric diagnoses. Subjects identified as cases by each method were often different subjects. Measured in terms of K, the chance-corrected degree of agreement between the DIS and psychiatrists' one-month diagnoses was moderate for DSM-III alcohol-use disorder (abuse and dependence combined), and lower for other mental disorder categories. The unreliability of either the DIS or psychiatric diagnoses is one potential explanation for the observed disagreements. Others include the following: (1) insufficient or inadequate information (on which to base a diagnosis); (2) recency of disorder; (3) incomplete criterion coverage; (4) overinclusive DIS questions; and (5) degree of reliance on subject symptom reports. Further study of the nature and sources of these discrepancies is underway. This work should produce a more complete understanding of obstacles to mental disorder case ascertainment by lay interview and clinical examination methods in the context of a field survey.

The Meaning of Cognitive Impairment in the Elderly

Abstract: In order to determine the meaning of cognitive impairment in community dwelling elderly, 3,481 adults were interviewed in their homes using the Mini-Mental State Examination. Ninety-six per cent of the population aged 18-64 scored 23 or higher, whereas 80 per cent of the population 65 and over scored 23 or higher. Individuals with low scores were suffering from a variety of psychiatric disorders including dementia. Thirty-three per cent of the elderly population scoring in the range of 0-23 had no diagnosable DSM-III condition. Prevalence of dementia from all causes was 6.1 per cent of the population over age 65. Two per cent of the population over age 65 were diagnosed as having Alzheimer's disease.

Quasicrystal with one-dimensional translational symmetry and a tenfold rotation axis.

Abstract: Studies of phase formation in rapidly solidified Al-Mn alloys (composition range 18-22 at.% Mn) show that an icosahedral phase is replaced by another noncrystallographic phase, a decagonal phase. The decagonal phase is another example of quasicrystal: It has a noncrystallographic point group ($\frac{10}{m}$ or $\frac{10}{\mathrm{mmm}}$) together with long-range orientational order and one-dimensional translational symmetry. The decagonal phase is an intermediate phase between an icosahedral phase and a crystal both from the symmetry and from the solidification condition points of view.

Identification of two lysosomal membrane glycoproteins.

Abstract: Two murine lysosome-associated membrane proteins, LAMP-1 of 105,000-115,000 D and LAMP-2 of 100,000-110,000 D, have been identified by monoclonal antibodies that bind specifically to lysosomal membranes. Both glycoproteins were distinguished as integral membrane components solubilized by detergent solutions but not by various chaotropic agents. The lysosome localization was demonstrated by indirect immunofluorescent staining, co-localization of the antigen to sites of acridine orange uptake, and immunoelectron microscopy. Antibody binding was predominantly located at the limiting lysosomal membrane, distinctly separated from colloidal gold-labeled alpha-2-macroglobulin accumulated in the lumen during prolonged incubation. LAMP-1 and LAMP-2 also appeared to be present in low concentrations on Golgi trans-elements but were not detected in receptosomes marked by the presence of newly endocytosed alpha-2-macroglobulin, or in other cellular structures. LAMP-1 and LAMP-2 were distinguished as different molecules by two-dimensional gel analysis, 125I-tryptic peptide mapping, and sequential immunoprecipitations of 125I-labeled cell extracts. Both glycoproteins were synthesized as a precursor protein of approximately 90,000 D, and showed a marked heterogeneity of apparent molecular weight expression in different cell lines. LAMP-2 was closely related or identical to the macrophage antigen, MAC-3, as indicated by antibody adsorption and tryptic peptide mapping. It is postulated that these glycoproteins, as major protein constituents of the lysosomal membrane, have important roles in lysosomal structure and function.

Comparison of low‐dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. A Controlled Clinical Trial

Abstract: One hundred eighty-nine patients with rheumatoid arthritis were entered into a prospective, controlled, double-blind multicenter trial comparing placebo and methotrexate (MTX). One hundred ten patients completed 18 weeks of therapy. No remissions were seen, but patients able to tolerate low-dose pulse MTX therapy were significantly improved, compared with patients receiving placebo therapy, for all clinical variables measured, including joint pain/tenderness and swelling counts, rheumatoid nodules, and patient and physician assessment of disease activity. MTX treatment demonstrated statistically significant improvement over placebo in patients with anemia, elevated erythrocyte sedimentation rate, and rheumatoid factor. However, nearly one-third of the patients receiving MTX were withdrawn for adverse drug reactions, of which elevated levels of liver enzymes was the most common. Pancytopenia occurred in 2 patients taking MTX. All adverse drug effects resolved without sequelae. MTX appears to be effective in the treatment of active rheumatoid arthritis but requires close monitoring for toxicity.

Optimal arterial resistance for the maximal stroke work studied in isolated canine left ventricle.

Abstract: In a previous analysis of ventricular arterial interaction (Sunagawa et al., 1983), we represented the left ventricle as an elastic chamber which periodically increases its volume elastance to a value equal to the slope of the linear end-systolic pressure-volume relationship. Similarly, the arterial load property was represented by an effective elastance which is the slope of the arterial end-systolic pressure-stroke volume relationship. Since the maximal transfer of potential energy from one elastic chamber to another occurs when they have equal elastance, we hypothesized that the left ventricle would do maximal external work if the ventricular elastance and the effective arterial elastance were equal. We tested this hypothesis in 10 isolated canine left ventricles, ejecting into a simulated arterial impedance, by extensively altering arterial resistance and finding the optimal resistance that maximized left ventricular stroke work under various combinations of end-diastolic volume, contractility, heart rate, and arterial compliance. Each of these parameters was set at one of three levels while others were at control. The optimal resistance varied only slightly with arterial compliance, whereas it varied widely with contractility and heart rate. We thus determined that the ratio of the optimal effective arterial elastance to the given ventricular elastance remained nearly unity. This result supports the hypothesis that the left ventricle does maximal external work to the arterial load when the ventricular and arterial elastances are equalized.