Showing papers by "Johns Hopkins University published in 1982"

Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain.

Abstract: Recent evidence indicates that the nucleus basalis of Meynert, a distinct population of basal forebrain neurons, is a major source of cholinergic innervation of the cerebral cortex. Postmortem studies have previously demonstrated profound reduction in the presynaptic markers for cholinergic neurons in the cortex of patients with Alzheimer's disease and senile dementia of the Alzheimer's type. The results of this study show that neurons of the nucleus basalis of Meynert undergo a profound (greater than 75 percent) and selective degeneration in these patients and provide a pathological substrate of the cholinergic deficiency in their brains. Demonstration of selective degeneration of such neurons represents the first documentation of a loss of a transmitter-specific neuronal population in a major disorder of higher cortical function and, as such, points to a critical subcortical lesion in Alzheimer's patients.

On the relations between the direction of two-dimensional arm movements and cell discharge in primate motor cortex

Abstract: The activity of single cells in the motor cortex was recorded while monkeys made arm movements in eight directions (at 45 degrees intervals) in a two-dimensional apparatus. These movements started from the same point and were of the same amplitude. The activity of 606 cells related to proximal arm movements was examined in the task; 323 of the 606 cells were active in that task and were studied in detail. The frequency of discharge of 241 of the 323 cells (74.6%) varied in an orderly fashion with the direction of movement. Discharge was most intense with movements in a preferred direction and was reduced gradually when movements were made in directions farther and farther away from the preferred one. This resulted in a bell-shaped directional tuning curve. These relations were observed for cell discharge during the reaction time, the movement time, and the period that preceded the earliest changes in the electromyographic activity (approximately 80 msec before movement onset). In about 75% of the 241 directionally tuned cells, the frequency of discharge, D, was a sinusoidal function of the direction of movement, theta: D = b0 + b1 sin theta + b2cos theta, or, in terms of the preferred direction, theta 0: D = b0 + c1cos (theta - theta0), where b0, b1, b2, and c1 are regression coefficients. Preferred directions differed for different cells so that the tuning curves partially overlapped. The orderly variation of cell discharge with the direction of movement and the fact that cells related to only one of the eight directions of movement tested were rarely observed indicate that movements in a particular direction are not subserved by motor cortical cells uniquely related to that movement. It is suggested, instead, that a movement trajectory in a desired direction might be generated by the cooperation of cells with overlapping tuning curves. The nature of this hypothetical population code for movement direction remains to be elucidated.

Isolation of intracellular membranes by means of sodium carbonate treatment: application to endoplasmic reticulum.

Abstract: A rapid and simple method for the isolation of membranes from subcellular organelles is described. The procedure consists of diluting the organelles in ice-cold 100 mM Na2CO3 followed by centrifugation to pellet the membranes. Closed vesicles are converted to open membrane sheets, and content proteins and peripheral membrane proteins are released in soluble form. Here we document the method by applying it to various subfractions of a rat liver microsomal fraction, prepared by continuous density gradient centrifugation according to Beaufay et al. (1974, J. Cell Biol. 61:213-231). The results confirm and extend those of previous investigators on the distribution of enzymes and proteins among the membranes of the smooth and rough endoplasmic reticulum. In the accompanying paper (1982, J. Cell Biol. 93:103-110) the procedure is applied to peroxisomes and mitochondria.

Optic Nerve Damage in Human Glaucoma: III. Quantitative Correlation of Nerve Fiber Loss and Visual Field Defect in Glaucoma, Ischemic Neuropathy, Papilledema, and Toxic Neuropathy

Abstract: The number and distribution of human optic nerve axons were compared with clinical measurements available the same eyes, including visual acuity, disc appearance, and visual field studies. Definite loss of axons occurs prior to reproducible visual field defects in some patients suspected of having glaucoma. In glaucoma, the superior and inferior poles of the nerve lose nerve fibers at a selectively greater rate, leading to an hourglass-shaped atrophy. Cavernous degeneration of the retrobulbar optic nerve is rarely observed in chronic glaucoma. The pattern of atrophy in examples of toxic amblyopia, ischemic optic neuropathy and chronic papilledema differ from that of glaucoma, suggesting different mechanisms of damage in these conditions.

Limits of the 'Mini-Mental State' as a screening test for dementia and delirium among hospital patients

Abstract: With a psychiatrist's standardized clinical diagnosis as the criterion, the 'Mini-Mental State' Examination (MMSE) was 87% sensitive and 82% specific in detecting dementia and delirium among hospital patients on a general medical ward. The false positive ratio was 39% and the false negative ratio was 5%. All false positives had less than 9 years of education; many were 60 years of age or older. Performance on specific MMSE items was related to education or age. These findings confirm the MMSE's value as a screen instrument for dementia and delirium when later, more intensive diagnostic enquiry is possible; they reinforce earlier suggestions that the MMSE alone cannot yield a diagnosis for these conditions.

Immunolocalization of keratin polypeptides in human epidermis using monoclonal antibodies.

Abstract: Three monoclonal antibodies (AE1, AE2, and AE3) were prepared against human epidermal keratins and used to study keratin expression during normal epidermal differentiation Immunofluorescence staining data suggested that the antibodies were specific for keratin-type intermediate filaments The reactivity of these antibodies to individual human epidermal keratin polypeptides (65-67, 58, 56, and 50 kdaltons) was determined by the immunoblot technique AE1 reacted with 56 and 50 kdalton keratins, AE2 with 65-67 and 56-kdalton keratins, and AE3 with 65-67 and 58 kdalton keratins Thus all major epidermal keratins were recognized by at least one of the monoclonal antibodies Moreover, common antigenic determinants were present in subsets of epidermal keratins To correlate the expression of specific keratins with different stages of in vivo epidermal differentiation, the antibodies were used for immunohistochemical staining of frozen skin sections AE1 reacted with epidermal basal cells, AE2 with cells above the basal layer, and AE3 with the entire epidermis The observation that AE1 and AE2 antibodies (which recognized a common 56 kdalton keratin) stained mutually exclusive parts of the epidermis suggested that certain keratin antigens must be masked in situ This was shown to be the case by direct analysis of keratins extracted from serial, horizontal skin sections using the immunoblot technique The results from these immunohistochemical and biochemical approaches suggested that: (a) the 65- to 67-kdalton keratins were present only in cells above the basal layer, (b) the 58-kdalton keratin was detected throughout the entire epidermis including the basal layer, (c) the 56-kdalton keratin was absent in the basal layer and first appeared probably in the upper spinous layer, and (d) the 50-kdalton keratin was the only other major keratin detected in the basal layer and was normally eliminated during s corneum formation The 56 and 65-67-kdalton keratins, which are characteristic of epidermal cells undergoing terminal differentiation, may be regarded as molecular markers for keratinization

Plural module medication delivery system

Abstract: A system consisting of a multiplicity of separate modules which collectively perform a useful biomedical purpose; the modules communicating with each other without the use of interconnecting wires. All modules may be intracorporeal or body mounted extracorporeal or some modules may be intracorporeal with others being body mounted extracorporeal. Signals are sent from one module to another by electromagnetic waves, by electrical signals using the body as an electrical conductor, or by acoustic waves. Physiologic sensor measurements sent from a first module causes a second module to perform some function in a closed-loop manner. One extracorporeal module can provide electrical power to an intracorporeal module; which power operates means for transferring data from the intracorporeal module to the body mounted extracorporeal module.

The Impact of Dementia on the Family

Abstract: To determine the impact of dementia on the family, we interviewed the primary care givers of 55 patients suffering from an irreversible dementia. Problems reported included disturbances of patient behavior such as catastrophic reactions, waking at night, suspiciousness, and communication disorders, some of which can be alleviated by physician-initiated intervention. Care givers also reported that they themselves had feelings of anger, depression, and fatigue, which can be treated as well. (JAMA1982;248:333-335)

Percutaneous balloon valvuloplasty: a new method for treating congenital pulmonary-valve stenosis.

Abstract: TRANSLUMINAL balloon angioplasty has been increasingly accepted as a nonsurgical technique for dilatation of stenotic arteries in the peripheral, renal, and coronary circulations.1 2 3 4 5 6 The ph...

Bent helical structure in kinetoplast DNA.

Abstract: We have investigated the unusual physical properties of a restriction fragment of Leishmania tarentolae kinetoplast DNA. A gel-purified fragment comprising slightly more than half of a minicircle was determined by Maxam-Gilbert sequence determination to be 490 base pairs (bp) in length. This fragment has dramatically anomalous electrophoretic behavior; it has an apparent size of 450 bp on a 1% agarose gel but migrates as 1,380 bp on a 12% polyacrylamide gel. However, in gel filtration on Sephacryl S-500, the fragment elutes with an apparent size of 375 bp. Finally, it behaves anomalously in electric dichroism experiments. Field-free rotational relaxation times from transient electric dichroism studies are highly sensitive to effective molecular dimensions. The rotational relaxation time of the kinetoplast fragment is smaller than that of a 309-bp control fragment from pBR322. Because rigorous control experiments rule out the possibility that this fragment is modified, these anomalous properties must be dictated by the sequence itself. Fragment behavior indicates that it has an unusually compact configuration; we propose that this molecule contains a region of systematically bent B-DNA. This model accounts for the fragment's difficulty in snaking through the pores of a polyacrylamide gel, its ease in diffusing into Sephacryl beads, and its smaller rotational relaxation time. Bending of this molecule may be caused by periodicities in the DNA sequence.

Gentrification and Uneven Development

Abstract: A debate is emerging over whether gentrification and urban redevelopment are temporary, ephemeral processes or only the beginning of a long-term restructuring of urban space. In order to assess the future of the inner city, it is necessary to understand the origins of the present redevelopment process, yet little or no theoretical work has been done. In fact, gentrification and urban redevelopment are the leading edge of a larger process of uneven development which is a specific process, rooted in the structure of the capitalist mode of production. According to this perspective, gentrification is only a small part of a restructuring of urban space which is, in turn, part of the wider economic restructuring necessitated by the present economic crisis.

Nonlinear theory of film rupture

Abstract: The present work aims at examining nonlinear effects on film rupture by investigating the stability of thin films to finite amplitude disturbances. The dynamics of the liquid film is formulated using the Navier-Stokes equations augmented by a body force describing the London/van der Waals attractions. The liquid film is assumed to be charge neutralized, nondraining, and laterally unbounded. A nonlinear evolution equation is derived for h ( x , t ), the film thickness. This strongly nonlinear partial differential equation is solved by numerical methods as part of an initial-value problem for periodic boundary conditions in x , the lateral space dimension. Given this model, one obtains true rupture in the sense that the film thickness becomes zero in a finite time. The results reveal rupture characteristics and effects of nonlinearities on the rupture properties.

Autoradiographic localization of adenosine receptors in rat brain using [3H]cyclohexyladenosine.

Abstract: Adenosine (A1) receptor binding sites have been localized in rat brain by an in vitro light microscopic autoradiographic method. The binding of [3H]N6-cyclohexyladenosine to slide-mounted rat brain tissue sections has the characteristics of A1 receptors. It is saturable with high affinity and has appropriate pharmacology and stereospecificity. The highest densities of adenosine receptors occur in the molecular layer of the cerebellum, the molecular and polymorphic layers of the hippocampus and dentate gyrus, the medial geniculate body, certain thalamic nuclei, and the lateral septum. High densities also are observed in certain layers of the cerebral cortex, the piriform cortex, the caudate-putamen, the nucleus accumbens, and the granule cell layer of the cerebellum. Most white matter areas, as well as certain gray matter areas, such as the hypothalamus, have negligible receptor concentrations. These localizations suggest possible central nervous system sites of action of adenosine.

Computed tomography of bronchiectasis.

Abstract: Computed tomography (CT) was performed on six patients with bronchiectasis. In two cases of advanced cystic bronchiectasis, the diagnosis was apparent on plain chest roentgenograms. In four cases, bronciectasis was initially diagnosed by CT and later confirmed by bronchography. The CT signs

Increased Brain Dopamine and Dopamine Receptors in Schizophrenia

Abstract: In postmortem samples of caudate nucleus and nucleus accumbens from 48 schizophrenic patients, there were significant increases in both the maximum number of binding sites (Bmax) and the apparent dissociation constant (KD) for tritiated spiperone. The increase in apparent KD probably reflects the presence of residual neuroleptic drugs, but changes in Bmax for tritiated spiperone reflect genuine changes in receptor numbers. The increases in receptors were seen only in patients in whom neuroleptic medication had been maintained until the time of death, indicating that they may be entirely iatrogenic. Dopamine measurements for a larger series of schizophrenic and control cases (n greater than 60) show significantly increased concentrations in both the nucleus accumbens and caudate nucleus. The changes in dopamine were not obviously related to neuroleptic medication and, unlike the receptor changes, were most severe in younger patients.

Heterogeneity in epidermal basal keratinocytes: morphological and functional correlations

Abstract: Two structurally distinct populations of basal keratinocytes, nonserrated and serrated, were observed in cynomolgus monkey and human palm epidermis. Anatomical location, fine structural features, and kinetic properties suggest that nonserrated cells represent a stem cell population and that serrated cells help anchor the epidermis to the dermis.

Polypeptide and phospholipid composition of the membrane of rat liver peroxisomes: comparison with endoplasmic reticulum and mitochondrial membranes.

Abstract: Membranes were isolated from highly purified peroxisomes, mitochondria, and rough and smooth microsomes of rat liver by the one-step Na2CO3 procedure described in the accompanying paper (1982, J. Cell Biol. 93:97-102). The polypeptide compositions of these membranes were determined by SDS PAGE and found to be greatly dissimilar. The peroxisomal membrane contains 12% of the peroxisomal protein and consists of three major polypeptides (21,700, 67,700 and 69,700 daltons) as well as some minor polypeptides. The major peroxisomal membrane proteins as well as most of the minor ones are absent from the endoplasmic reticulum (ER). Conversely, most ER proteins are absent from peroxisomes. By electron microscopy, purified peroxisomal membranes are approximately 6.8 nm thick and have a typical trilaminar appearance. The phospholipid/protein ratio of peroxisomal membranes is approximately 200 nmol/mg; the principal phospholipids are phosphatidyl choline and phosphatidyl ethanolamine as in ER and mitochondrial membranes. In contrast to the mitochondria, peroxisomal membranes contain no cardiolipin. All the membranes investigated contain a polypeptide band with a molecular mass of approximately 15,000 daltons. Whether this represents an exceptional common membrane protein or a coincidence is unknown. The implications of these results for the biogenesis of peroxisomes are discussed.

Functional Activities of Autoantibodies to Acetylcholine Receptors and the Clinical Severity of Myasthenia Gravis

Abstract: The pathogenesis of myasthenia gravis involves a humorally mediated autoimmune attack directed against acetylcholine receptors of skeletal muscles. Antibodies against acetylcholine receptors are detected in the serum of more than 80 per cent of patients, but the antibody titers correspond poorly with the severity of disease. To distinguish between antibody titers and antibody activity, we measured the ability of serum immunoglobulin from 49 patients to induce accelerated degradation or blockade of the binding sites of acetylcholine receptors, using a mammalian skeletal-muscle tissue-culture system. Immunoglobulin from 41 of 45 patients tested (91 per cent) increased the rate of degradation of acetylcholine receptors, and the relative increase in the degradation rate corresponded closely (P less than 0.001) with clinical status. Immunoglobulin from 42 of 48 patients tested (88 per cent) produced blockade of receptors, and the extent of the blockade also corresponded with clinical status (P less than 0.001). An index of the combined activities of the immunoglobulin in accelerating degradation and producing blockade of acetylcholine receptors was elevated in 43 of 44 patients (98 per cent) whose immunoglobulins were tested for both activities; this index predicted the patients' clinical status significantly better (P less than 0.001) than either measure alone. This finding suggests that the functional ability of antibodies to decrease the number of available acetylcholine receptors by these two mechanisms is clinically relevant in the pathogenesis of myasthenia gravis.

Nonrandom association of polymorphic restriction sites in the β-globin gene cluster

Abstract: By using probes for e-, Ψβ1-, and β-globin genes, we found four additional polymorphic restriction sites that have frequencies >0.1 in persons of Mediterranean area origin, Asian Indians, and American Blacks. Three of these (HincII sites) and the two previously described polymorphic HindIII sites [one in intervening sequence (IVS) II of each γ-globin gene] are distributed over 32 kilobases (kb) of DNA located 5′ to the δ-globin gene. This region of DNA comprises two-thirds of the β-globin gene cluster. Since each of these five polymorphic sites can be present (+) or absent (-), in theory there exist 32 possible combinations of sites (haplotypes). However, in Italians, Greeks, Indians, and Turks, 3 of the 32 haplotypes, (+----), (-+-++), and (-++-+), account for 92% of 89 βA chromosomes examined. The observed frequencies for these haplotypes are 0.64, 0.15, and 0.13 in the populations studied, in contrast to expected frequencies (based on the observed gene frequencies at each of the five sites) of 0.20, 0.006, and 0.005, respectively. In American Blacks, a fourth haplotype, (----+), which is rare in non-Black populations, has a frequency of 0.37 in contrast to its expected frequency of 0.05. These results suggest a nonrandom association of DNA sequences over 32 kb 5′ to the δ-globin gene in all populations studied. Two other polymorphic sites 3′ to the δ gene (the newly discovered Ava II site in IVS II of the β-globin gene and the BamHI site 3′ to it) are nonrandomly associated with each other but randomly distributed with respect to the above haplotypes. This suggests that randomization of sequences has occurred within 12 kb of DNA between these two nonrandomly associated sequence clusters. Nonrandom association of polymorphic restriction sites has practical consequences in that it limits the usefulness of these additional HincII sites for prenatal diagnosis of hemoglobinopathies by linkage analysis. These sites provide little additional information for detection of β-thalassemia, while the polymorphic Ava II site, which lies outside the nonrandomly associated sequences 5′ to the δ gene, improves the test applicability from 52% to 70% of couples at risk.

Parent Involvement: A Survey of Teacher Practices

Abstract: The Elementary School Journal Volume 83, Number 2 ? 1982 by The University of Chicago. All rights reserved. 001 3-5984183/8302-0009$01o.00 Teachers approach their instructional tasks with a variety of perspectives and strategies that emphasize certain aspects of teaching and deemphasize others. For example, some teachers teach language skills using organized games, while other teachers teach the same skills by direct instruction. Teachers adopt different approaches to the same subject matter partly because their teaching situations differ. Their students may have different learning problems or their classrooms may have varied resources and facilities. Even in the

Student suspension: A critical reappraisal

Abstract: This paper analyzes national level data, gathered for the Safe School Study, to directly address the question, “Why are students suspended from school?” Data are available on students in both junior and senior high schools from a representative sample of the nation's schools. Using a range of analytical techniques, the paper attempts to tease out the relationships between (1) student misbehavior at varying types of schools and suspension rates, (2) the effects of teacher judgments and attitudes, (3) the effect of administrative structures, (4) the effect of perceived academic potential, and (5) the effect of racial bias. It is concluded that suspension rates cannot be regarded as a simple reflection of student misbehavior in school, but rather as the result of a complex of factors grounded in the ways schools operate. Suspension rates are best predicted by (1) knowing the kind of school a student went to, and (2) knowing how that school was run.

Sites of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells.

Abstract: Previous work has shown that injury of neoplastic cells by cytotoxic macrophages (CM) in cell culture is accompanied by inhibition of mitochondrial respiration. We have investigated the nature of this inhibition by studying mitochondrial respiration in CM-injured leukemia L1210 cells permeabilized with digitonin. CM-induced injury affects the mitochondrial respiratory chain proper. Complex I (NADH-coenzyme Q reductase) and complex II (succinate-coenzyme Q reductase) are markedly inhibited. In addition a minor inhibition of cytochrome oxidase was found. Electron transport from alpha-glycerophosphate through the respiratory chain to oxygen is unaffected and permeabilized CM-injured L1210 cells oxidizing this substrate exhibit acceptor control. However, glycerophosphate shuttle activity was found not to occur within CM-injured or uninjured L1210 cells in culture hence, alpha-glycerophosphate is apparently unavailable for mitochondrial oxidation in the intact cell. It is concluded that the failure of respiration of intact neoplastic cells injured by CM is caused by the nearly complete inhibition of complexes I and II of the mitochondrial electron transport chain. The time courses of CM-induced electron transport inhibition and arrest of L1210 cell division are examined and the possible relationship between these phenomena is discussed.

Viral etiology of juvenile- and adult-onset squamous papilloma of the larynx.

Abstract: Juvenile- and adult-onset laryngeal papillomas were examined for the presence of a human papillomavirus (HPV) genome and capsid antigens. DNA was isolated from a portion of tissue removed for therapeutic purposes, and the presence of a papillomavirus genome was detected by Southern transfer analysis. The viral DNA found in the 12 juvenile-onset and the 8 adult-onset laryngeal papillomas examined was identified as HPV-6 on the basis of size, restriction endonuclease digestion patterns, and homology detected under stringent conditions. Restriction endonuclease analysis of the viral genomes revealed at least four different subtypes, designated HPV-6c through HPV-6f. The most common subtype, HPV-6c, was detected in over half of the papillomas studied, including both juvenile and adult types. The remaining tissue was fixed and processed for immunocytochemistry. The immunoperoxidase technique was used with an antiserum that reacts with capsid antigen(s) common to all HPV serotypes. HPV antigen was found in two of the juvenile-onset papillomas and two of the adult-onset papillomas. The antigen was localized to the nucleus and was distributed in the superficial layers of the epithelium. HPV capsid antigen had not previously been detected in cases of adult-onset papilloma, and the HPV genome in both juvenile- and adult-onset laryngeal papillomas had not been characterized. Despite the absence of detectable viral antigen in most of the specimens examined, the presence of the HPV genome provides strong evidence for the papillomavirus etiology of these tumors.

Quantitative Studies of Retinal Nerve Fiber Layer Defects

Abstract: • We compared the clinical appearance of the retinal nerve fiber layer (NFL) and its histology in primate eyes. In 12 eyes with NFL lesions induced by orbital optic nerve trauma, clinical detection of NFL atrophy was possible after loss of 50% of the neural tissue in a given area. Some retinal areas with no visible NFL striations had remaining nerve fibers. The detectability of NFL atrophy was directly affected both by the pattern of nerve fiber loss as well as by the zone of the retina in which the loss occurred. While each nerve bundle gives rise to a single light striation nasal and temporal to the nerve head, this one-to-one correspondence is not true above and below the disc, where bundles are thicker and incompletely divided by glial septa.

The Effect of Treatment on Mortality in Mild Hypertension: Results of the Hypertension Detection and Follow-up Program

Abstract: In the Hypertension Detection and Follow-up Program, 7825 (71.5 per cent) of the 10,940 participants had diastolic blood pressures averaging between 90 and 104 mm Hg on entry into the study and were designated Stratum 1. Half were referred to their usual source of care in the community (the referred-care group), and half were treated intensively in special clinics (the stepped-care group). Five-year mortality in the Stratum 1 patients given stepped care was 20.3 per cent lower than in those given referred care (P less than 0.01). Particularly noteworthy was the beneficial effect of stepped-care treatment on persons with diastolic pressures of 90 to 104 mm Hg who had no evidence of end-organ damage and were not receiving antihypertensive medication when they entered the study. This subgroup had 28.6 per cent fewer deaths at five years among those treated with stepped care than among those treated with referred care (P less than 0.01). These findings support a recommendation that in patients with mild hypertension, treatment should be considered early, before damage to end organs occurs.