Showing papers by "Johns Hopkins University published in 1990"

Localization of nitric oxide synthase indicating a neural role for nitric oxide

Abstract: Nitric oxide (NO), apparently identical to endothelium-derived relaxing factor in blood vessels, is also formed by cytotoxic macrophages, in adrenal gland and in brain tissue, where it mediates the stimulation by glutamate of cyclic GMP formation in the cerebellum Stimulation of intestinal or anococcygeal nerves liberates NO, and the resultant muscle relaxation is blocked by arginine derivatives that inhibit NO synthesis It is, however, unclear whether in brain or intestine, NO released following nerve stimulation is formed in neurons, glia, fibroblasts, muscle or blood cells, all of which occur in proximity to neurons and so could account for effects of nerve stimulation on cGMP and muscle tone We have now localized NO synthase protein immunohistochemically in the rat using antisera to the purified enzyme We demonstrate NO synthase in the brain to be exclusively associated with discrete neuronal populations NO synthase is also concentrated in the neural innervation of the posterior pituitary, in autonomic nerve fibres in the retina, in cell bodies and nerve fibres in the myenteric plexus of the intestine, in adrenal medulla, and in vascular endothelial cells These prominent neural localizations provide the first conclusive evidence for a strong association of NO with neurons

The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip.

Abstract: Clinical criteria for the classification of patients with hip pain associated with osteoarthritis (OA) were developed through a multicenter study. Data from 201 patients who had experienced hip pain for most days of the prior month were analyzed. The comparison group of patients had other causes of hip pain, such as rheumatoid arthritis or spondylarthropathy. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop different sets of criteria to serve different investigative purposes. Multivariate methods included the traditional "number of criteria present" format and "classification tree" techniques. Clinical criteria: A classification tree was developed, without radiographs, for clinical and laboratory criteria or for clinical criteria alone. A patient was classified as having hip OA if pain was present in combination with either 1) hip internal rotation greater than or equal to 15 degrees, pain present on internal rotation of the hip, morning stiffness of the hip for less than or equal to 60 minutes, and age greater than 50 years, or 2) hip internal rotation less than 15 degrees and an erythrocyte sedimentation rate (ESR) less than or equal to 45 mm/hour; if no ESR was obtained, hip flexion less than or equal to 115 degrees was substituted (sensitivity 86%; specificity 75%). Clinical plus radiographic criteria: The traditional format combined pain with at least 2 of the following 3 criteria: osteophytes (femoral or acetabular), joint space narrowing (superior, axial, and/or medial), and ESR less than 20 mm/hour (sensitivity 89%; specificity 91%). The radiographic presence of osteophytes best separated OA patients and controls by the classification tree method (sensitivity 89%; specificity 91%). The "number of criteria present" format yielded criteria and levels of sensitivity and specificity similar to those of the classification tree for the combined clinical and radiographic criteria set. For the clinical criteria set, the classification tree provided much greater specificity. The value of the radiographic presence of an osteophyte in separating patients with OA of the hip from those with hip pain of other causes is emphasized.

Reversal of experimental parkinsonism by lesions of the subthalamic nucleus

Abstract: Although it is known that Parkinson's disease results from a loss of dopaminergic neurons in the substantia nigra, the resulting alterations in activity in the basal ganglia responsible for parkinsonian motor deficits are still poorly characterized. Recently, increased activity in the subthalamic nucleus has been implicated in the motor abnormalities. To test this hypothesis, the effects of lesions of the subthalamic nucleus were evaluated in monkeys rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The lesions reduced all of the major motor disturbances in the contralateral limbs, including akinesia, rigidity, and tremor. This result supports the postulated role of excessive activity in the subthalamic nucleus in Parkinson's disease.

Suppression of human colorectal carcinoma cell growth by wild-type p53.

Abstract: Mutations of the p53 gene occur commonly in colorectal carcinomas and the wild-type p53 allele is often concomitantly deleted. These findings suggest that the wild-type gene may act as a suppressor of colorectal carcinoma cell growth. To test this hypothesis, wild-type or mutant human p53 genes were transfected into human colorectal carcinoma cell lines. Cells transfected with the wild-type gene formed colonies five- to tenfold less efficiently than those transfected with a mutant p53 gene. In those colonies that did form after wild-type gene transfection, the p53 sequences were found to be deleted or rearranged, or both, and no exogenous p53 messenger RNA expression was observed. In contrast, transfection with the wild-type gene had no apparent effect on the growth of epithelial cells derived from a benign colorectal tumor that had only wild-type p53 alleles. Immunocytochemical techniques demonstrated that carcinoma cells expressing the wild-type gene did not progress through the cell cycle, as evidenced by their failure to incorporate thymidine into DNA. These studies show that the wild-type gene can specifically suppress the growth of human colorectal carcinoma cells in vitro and that an in vivo-derived mutation resulting in a single conservative amino acid substitution in the p53 gene product abrogates this suppressive ability.

Identification of a chromosome 18q gene that is altered in colorectal cancers

Abstract: Allelic deletions involving chromosome 18q occur in more than 70 percent of colorectal cancers. Such deletions are thought to signal the existence of a tumor suppressor gene in the affected region, but until now a candidate suppressor gene on this chromosomal arm had not been identified. A contiguous stretch of DNA comprising 370 kilobase pairs (kb) has now been cloned from a region of chromosome 18q suspected to reside near this gene. Potential exons in the 370-kb region were defined by human-rodent sequence identities, and the expression of potential exons was assessed by an "exon-connection" strategy based on the polymerase chain reaction. Expressed exons were used as probes for cDNA screening to obtain clones that encoded a portion of a gene termed DCC; this cDNA was encoded by at least eight exons within the 370-kb genomic region. The predicted amino acid sequence of the cDNA specified a protein with sequence similarity to neural cell adhesion molecules and other related cell surface glycoproteins. While the DCC gene was expressed in most normal tissues, including colonic mucosa, its expression was greatly reduced or absent in most colorectal carcinomas tested. Somatic mutations within the DCC gene observed in colorectal cancers included a homozygous deletion of the 5' end of the gene, a point mutation within one of the introns, and ten examples of DNA insertions within a 0.17-kb fragment immediately downstream of one of the exons. The DCC gene may play a role in the pathogenesis of human colorectal neoplasia, perhaps through alteration of the normal cell-cell interactions controlling growth.

Finite-dimensional variational inequality and nonlinear complementarity problems: a survey of theory, algorithms and applications

Abstract: Over the past decade, the field of finite-dimensional variational inequality and complementarity problems has seen a rapid development in its theory of existence, uniqueness and sensitivity of solution(s), in the theory of algorithms, and in the application of these techniques to transportation planning, regional science, socio-economic analysis, energy modeling, and game theory. This paper provides a state-of-the-art review of these developments as well as a summary of some open research topics in this growing field.

Abrupt visual onsets and selective attention: voluntary versus automatic allocation.

Abstract: The hypothesis that abrupt visual onsets capture attention automatically, as suggested by Yantis and Jonides (1984) was tested in four experiments. A centrally located cue directed attention to one of several stimulus positions in preparation for the identification of a target letter embedded in an array of distractor letters. In all experiments, one stimulus (either the target or one of the distractors) had an abrupt onset; the remaining letters did not. The effectiveness of the cue was manipulated (varying either its duration or its predictive validity) to test whether abrupt onsets capture attention even when subjects are in a highly focused attentional state. Results showed that onsets do not necessarily capture attention in violation of an observer's intentions. A mechanism for partially automatic attentional capture by abrupt onset is proposed, and the diagnosticity of the intentionality criterion for automaticity is discussed.

The existence of publication bias and risk factors for its occurrence.

Abstract: Publication bias is the tendency on the parts of investigators, reviewers, and editors to submit or accept manuscripts for publication based on the direction or strength of the study findings. Much of what has been learned about publication bias comes from the social sciences, less from the field of medicine. In medicine, three studies have provided direct evidence for this bias. Prevention of publication bias is important both from the scientific perspective (complete dissemination of knowledge) and from the perspective of those who combine results from a number of similar studies (meta-analysis). If treatment decisions are based on the published literature, then the literature must include all available data that is of acceptable quality. Currently, obtaining information regarding all studies undertaken in a given field is difficult, even impossible. Registration of clinical trials, and perhaps other types of studies, is the direction in which the scientific community should move. (JAMA. 1990;263:1385-1389)

On the nature and implications of starburst-driven galactic superwinds

Abstract: Optical spectroscopic data are presented on the ionized nebulae associated with 14 galaxies that are strong far-IR emitters. It is found that the data provide both qualitative and quantitative support for the 'superwind' model in which the kinetic energy provided by SNe and winds from massive stars in a central starburst drives a large-scale outflow that can shock heat and accelerate ambient interstellar and circumgalactic gas. Clear kinematic signatures of an outflow along the galaxy's minor axis are found for the three nearest far-IR galaxies (FIRGs). The FIRG nebulae are highly overpressured relative to the Galactic ISM, with the pressure dropping systematically with distance from the nucleus. Superwinds are energetically adequate to power both the observed optical and X-ray nebulae, and the relative emission-line intensities and their radial variations are consistent with ionization by wind-driven shocks, but not with photoionization by normal O stars or an AGN. The possible astrophysical implications of superwinds are discussed.

“Components Separation” Method for Closure of Abdominal-Wall Defects: An Anatomic and Clinical Study

Abstract: Closure of large abdominal-wall defects usually requires the transposition of remote myocutaneous flaps or free-tissue transfers. The purpose of this study was to determine if separation of the muscle components of the abdominal wall would allow mobilization of each unit over a greater distance than possible by mobilization of the entire abdominal wall as a block. The abdominal walls of 10 fresh cadavers were dissected. This demonstrated that the external oblique muscle can be separated from the internal oblique in a relatively avascular plane. The rectus muscle with its overlying rectus fascia can be elevated from the posterior rectus sheath. The compound flap of the rectus muscle, with its attached internal oblique-transversus abdominis muscle, can be advanced 10 cm around the waistline. The external oblique has limited advancement. These findings were utilized clinically in the reconstruction of abdominal-wall defects in 11 patients, ranging in size from 4 x 4 to 18 x 35 cm. This study suggests that large abdominal-wall defects can be reconstructed with functional transfer of abdominal-wall components without the need for resorting to distant transposition of free-muscle flaps.

Zidovudine in Asymptomatic Human Immunodeficiency Virus Infection: A Controlled Trial in Persons with Fewer Than 500 CD4-Positive Cells per Cubic Millimeter

Abstract: Zidovudine (AZT) is a potent inhibitor of the replication of the human immunodeficiency virus (HIV), and it has been shown to improve survival in advanced HIV disease. We conducted a randomized, double-blind trial in adults with asymptomatic HIV infection who had CD4+ cell counts of fewer than 500 per cubic millimeter on entry into the study. The subjects (92 percent male) were randomly assigned to one of three treatment groups: placebo (428 subjects); zidovudine, 500 mg per day (453); or zidovudine, 1500 mg per day (457). After a mean follow-up of 55 weeks (range, 19 to 107), 33 of the subjects assigned to placebo had the acquired immunodeficiency syndrome (AIDS), as compared with 11 of those assigned to receive 500 mg of zidovudine (P = 0.002; relative risk, 2.8; 95 percent confidence interval, 1.4 to 5.6) and 14 of those assigned to receive 1500 mg of zidovudine (P = 0.05; relative risk, 1.9; 95 percent confidence interval, 1.0 to 3.5). In the three treatment groups, the rates of progression (per 100 person-years) to either AIDS or advanced AIDS-related complex were 7.6, 3.6, and 4.3, respectively. As compared with those assigned to placebo, the subjects in the zidovudine groups had significant increases in the number of CD4+ cells and significant declines in p24 antigen levels. In the 1500-mg zidovudine group, severe hematologic toxicity (anemia or neutropenia) was more frequent than in the other groups (P less than 0.0001). In the 500-mg zidovudine group, nausea was the only toxicity that was significantly more frequent (in 3.3 percent) than in the placebo group (P = 0.001). We conclude that zidovudine is safe and effective in persons with asymptomatic HIV infection and fewer than 500 CD4+ cells per cubic millimeter. Additional study will be required to determine whether such treatment will ultimately improve survival for persons infected with HIV.

p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis.

Abstract: Coordinate loss of one copy of the p53 gene and mutation of the remaining copy occur in colorectal carcinomas and in many other human malignancies. However, the prevalence of p53 gene mutations in carcinomas which maintain both parental copies of p53 has not previously been evaluated. Moreover, it is not known whether p53 gene mutations are limited to malignant tumors or whether they can also occur in benign neoplasms. To answer these questions, a total of 58 colorectal tumors have been examined; in each tumor, allelic losses were assessed using restriction fragment length polymorphisms and p53 gene mutations were assessed by sequencing cloned polymerase chain reaction products. The following conclusions emerged: (a) p53 gene mutations occurred but were relatively rare in adenomas, regardless of size and whether the adenomas were derived from patients with familial adenomatous polyposis; (b) In carcinomas as well as in adenomas, p53 gene mutations were infrequently observed in tumors which contain both copies of chromosome 17p (17% of 30 tumors), while tumors which lost one copy of chromosome 17p usually had a mutation in the remaining p53 allele (86% of 28 tumors); (c) p53 gene mutations were found at similar frequencies in primary tumor samples and in cell lines derived from tumors. These and other data suggest that the rate limiting step in p53 inactivation is point mutation and that once a mutation occurs, loss of the remaining wild-type allele rapidly follows. Both mutations and allelic losses generally occur near the transition from benign to malignant growth, and the p53 gene may play a causal role in this progression.

Taxol: A Novel Investigational Antimicrotubule Agent

Abstract: Microtubules are among the most strategic subcellular targets of anticancer chemotherapeutics. Despite this fact, new antimicrotubule agents that possess unique mechanisms of cytotoxic action and have broader antineoplastic spectra than the vinca alkaloids have not been introduced over the last several decades--until the recent development of taxol. Unlike classical antimicrotubule agents like colchicine and the vinca alkaloids, which induce depolymerization of microtubules, taxol induces tubulin polymerization and forms extremely stable and nonfunctional microtubules. Taxol has demonstrated broad activity in preclinical screening studies, and antineoplastic activity has been observed in several classically refractory tumors. These tumors include cisplatin-resistant ovarian carcinoma in phase II trials and malignant melanoma and non-small cell lung carcinoma in phase I studies. Taxol's structural complexity has hampered the development of feasible processes for synthesis, and its extreme scarcity has limited the use of a conventional, broad-scale screening approach for evaluation of clinical antitumor activity. However, taxol's unique mechanism of action, its spectrum of preclinical antitumor activity, and tumor responses in early clinical trials have generated renewed interest in pursuing its development.

Higher Algebraic K-Theory of Schemes and of Derived Categories

Abstract: In this paper we prove a localization theorem for the K-theory of commutative rings and of schemes, Theorem 7.4, relating the K-groups of a scheme, of an open subscheme, and of the category of those perfect complexes on the scheme which are acyclic on the open subscheme. The localization theorem of Quillen [Q1] for K′- or G-theory is the main support of his many results on the G-theory of noetherian schemes. The previous lack of an adequate localization theorem for K-theory has obstructed development of this theory for the fifteen years since 1973. Hence our theorem unleashes a pack of new basic results hitherto known only under very restrictive hypotheses like regularity. These new results include the “Bass fundamental theorem” 6.6, the Zariski (Nisnevich) cohomolog-ical descent spectral sequence that reduces problems to the case of local (hensel local) rings 10.3 and 19.8, the Mayer-Vietoris theorem for open covers 8.1, invariance mod l under polynomial extensions 9.5, Vorst-van der Kallen theory for NK 9.12, Goodwillie and Ogle-Weibel theorems relating K-theory to cyclic cohomology 9.10, mod l Mayer-Vietoris for closed covers 9.8, and mod l comparison between algebraic and topological K-theory 11.5 and 11.9. Indeed most known results in K-theory can be improved by the methods of this paper, by removing now unnecessary regularity, affineness, and other hypotheses.

The Origins of American Social Science

Abstract: Introduction Part I. European Social Science in Antebellum America: 1. The discovery of modernity 2. The American exceptionalist vision Part II. The Crisis of American Exceptionalism, 1865-1896: 3. Establishment of the social science disciplines 4. The threat of socialism in economics and sociology Part III. Progressive Social Science, 1896-1914: 5. The liberal revision of American exceptionalism 6. Marginalism and historicism in economics 7. Toward a sociology of social control 8. From historico-politics to political science Part IV. American Social Science As The Study Of Natural Process, 1908-1929: 9. Modernist historical consciousness and American liberal change 10. The advent of scientism Epilogue Footnote abbreviations Footnotes.

Paraneoplastic Pemphigus: An Autoimmune Mucocutaneous Disease Associated with Neoplasia

Abstract: BACKGROUND AND METHODS We describe five patients with underlying neoplasms in whom painful mucosal ulcerations and polymorphous skin lesions developed, usually with progression to blistering eruptions on the trunk and extremities. Histologic examination showed vacuolization of epidermal basal cells, keratinocyte necrosis, and acantholysis. Immunofluorescence testing revealed atypical pemphigus-like autoantibodies in perilesional epithelium and serum from all five patients. We studied the antigenic specificities of the autoantibodies by indirect immunofluorescence and immunoprecipitation, using extracts of 14C-labeled human keratinocytes. IgG purified from the serum of one patient was passively transferred to four neonatal mice to test for pathogenicity. RESULTS Immunofluorescence testing showed that the autoantibodies bound to the surface of tissues containing desmosomes, including complex and simple epithelia, and myocardium. An identical and unique complex of four polypeptides with molecular weights of 250, 230, 210, and 190 was immunoprecipitated by all serum samples. The 250-kd polypeptide comigrated with desmoplakin I (a protein found in the desmosomes of all epithelia), and the 230-kd antigen comigrated with the antigen of bullous pemphigoid. Cutaneous blisters, a positive Nikolsky's sign, and epidermal and esophageal acantholysis developed in all mice into which the autoantibody was injected. Electron microscopy showed epidermal acantholysis similar to lesions of experimentally induced pemphigus vulgaris. CONCLUSION These five patients with cancer had a novel acantholytic mucocutaneous disease characterized by autoantibodies that were pathogenic after passive transfer. The autoantibodies from these patients reacted with an antigen complex composed of desmoplakin I and the 230-kd antigen of bullous pemphigoid and two as yet unidentified epithelial antigens. We suggest the term "paraneoplastic pemphigus" for this disease.

Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia

Abstract: The authors' magnetic resonance imaging study of young schizophrenic demonstrates smaller volume of the superior temporal gyrus and of the left amygdala

Psychiatric symptoms and nursing home placement of patients with Alzheimer's disease

Abstract: Two hundred ten community-dwelling patients with Alzheimer's disease were examined prospectively by psychiatrists as part of a longitudinal study. Twenty-five of these patients who were institutionalized during the next 3 years were then matched to 25 patients who were not institutionalized, and the groups were compared. The patients who had been institutionalized had higher scores on standardized psychiatric rating scales but not on formal neuropsychological tests of cognition. These results suggest that potentially treatable (noncognitive) behavioral and psychiatric symptoms are risk factors for institutionalization, and that treating these symptoms might delay or prevent institutionalization of some patients.

Family history and the risk of prostate cancer.

Abstract: A case-control study was performed to estimate the relative risk of developing prostate cancer for men with a positive family history. Extensive cancer pedigrees were obtained on 691 men with prostate cancer and 640 spouse controls. Fifteen percent of the cases but only 8% of the controls had a father or brother affected with prostate cancer (P < .001). Men with a father or brother affected were twice as likely to develop prostate cancer as men with no relatives affected. In addition, there was a trend of increasing risk with increasing number of affected family members such that men with two or three first degree relatives affected had a five and 11–fold increased risk of developing prostate cancer. Recognizing that 9–10% of U.S. men will develop prostate cancer in their lifetime, men with a family history of prostate cancer should be advised of their significantly increased prostate cancer risk and should undergo appropriate screening measures for this disease.

Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis

Abstract: Recently, the excitatory amino acid neurotransmitter glutamate was implicated in the pathogenesis of a variety of chronic degenerative neurological diseases in humans and animals. This report describes abnormalities in excitatory amino acids in the central nervous system of 18 patients with amyotrophic lateral sclerosis (ALS). The concentration of the excitatory amino acids glutamate and aspartate in the cerebrospinal fluid were increased significantly (p less than 0.01) by 100 to 200% in patients with ALS. Similarly, the concentrations of the excitatory neuropeptide N-acetyl-aspartyl glutamate and its metabolite, N-acetyl-aspartate, were elevated twofold to threefold in the cerebrospinal fluid from the patients. There was no relationship between amino acid concentrations and duration of disease, clinical impairment, or patient age. In the ventral horns of the cervical region of the spinal cord, the level of N-acetyl-aspartyl glutamate and N-acetyl-aspartate was decreased by 60% (p less than 0.05) and 40% (p less than 0.05), respectively, in 8 patients with ALS. Choline acetyltransferase activity was also diminished by 35% in the ventral horn consistent with motor neuron loss. We conclude that excitatory amino acid metabolism is altered in patients with ALS. Based on neurodegenerative disease models, these changes may play a role in motor neuron loss in ALS.

Decreased erythropoietin response in patients with the anemia of cancer.

Abstract: Patients with solid tumors are often anemic even before they undergo cytotoxic therapy. Since the cause of the anemia of cancer is unknown, we examined the possible role of erythropoietin. Using a sensitive radioimmunoassay, we determined serum immunoreactive erythropoietin levels in 81 anemic patients with solid tumors. For any given degree of anemia, the serum concentration of immunoreactive erythropoietin was lower in this group of patients than in a group of control patients with iron-deficiency anemia (P = 0.0001). Furthermore, the expected inverse linear relation between serum levels of immunoreactive erythropoietin and of hemoglobin was absent in the group with cancer. The erythropoietin response was further decreased in patients receiving chemotherapy; it was not influenced by the presence or absence of cisplatin in the treatment regimen. The inability of the patients with cancer to produce erythropoietin was not absolute; if they had hypoxemia, adequate erythropoietin production was restored. We conclude that erythropoietin levels are inappropriately low in anemia associated with cancer, and that erythropoietin deficiency may contribute to the development of this form of anemia. Treatment of the anemia of cancer with erythropoietin may be of value.

Shear flow near solids: Epitaxial order and flow boundary conditions.

Abstract: We report on molecular-dynamics simulations of Lennard-Jones liquids sheared between two solid walls. The velocity fields, flow boundary conditions, and fluid structure were studied for a variety of wall and fluid properties. A broad spectrum of boundary conditions was observed including slip, no-slip, and locking. We show that the degree of slip is directly related to the amount of structure induced in the fluid by the periodic potential from the solid walls. For weak wall-fluid interactions there is little ordering and slip was observed. At large interactions, substantial epitaxial ordering was induced and the first one or two fluid layers became locked to the wall. This epitaxial ordering was enhanced when the wall and fluid densities were equal. For unequal densities, high-order commensurate structures formed in the first fluid layer creating slip within the fluid.

The expression and posttranslational modification of a neuron-specific β-tubulin isotype during chick embryogenesis

Abstract: Five β-tubulin isotypes are expressed differentially during chicken brain development. One of these isotypes is encoded by the gene cβ4 and has been assigned to an isotypic family designated as Class III (βIII). In the nervous system of higher vertebrates, βIII is synthesized exclusively by neurons. A βIII-specific monoclonal antibody was used to determine when during chick embryogenesis cβ4 is expressed, the cellular localization of βIII, and the number of charge variants (isoforms) into which βIII can be resolved by isoelectric focusing. On Western blots, βIII is first detectable at stages 12–13. Thereafter, the relative abundance of βIII in brain increases steadily, apparently in conjunction with the rate of neural differentiation. The isotype was not detectable in non-neural tissue extracts from older embryos (days 10–14) and hatchlings. Western blots of protein separated by two-dimensional gel electrophoresis (2D–PAGE) reveal that the number of βIII isoforms increases from one to three during neural development. This evidence indicates that βIII is a substrate for developmentally regulated, multiple-site posttranslational modification. Immunocytochemical studies reveal that while cβ4 expression is restricted predominantly to the nervous system, it is transiently expressed in some embryonic structures. More importantly, in the nervous system, immunoreactive cells were located primarily in the non-proliferative marginal zone of the neural epithelia. Regions containing primarily mitotic neuroblasts were virtually unstained. This localization pattern indicates that cβ4 expression occurs either during or immediately following terminal mitosis, and suggests that βIII may have a unique role during early neuronal differentiation and neurite outgrowth.

Blindness and Visual Impairment in an American Urban Population: The Baltimore Eye Survey

Abstract: Data on the prevalence of blindness and visual impairment in multiracial urban populations of the United States are not readily available. The Baltimore Eye Survey was designed to address this lack of information and provide estimates of prevalence in age-race subgroups that had not been well studied in the past. A population-based sample of 5300 blacks and whites from east Baltimore, Md, received an ophthalmologic screening examination that included detailed visual acuity measurements. Blacks had, on average, a twofold excess prevalence of blindness and visual impairment than whites, irrespective of definition. Rates rose dramatically with age for all definitions of vision loss, but there was no difference in prevalence by sex. More than 50% of subjects improved their presenting vision after refractive correction, with 7.5% improving three or more lines. Rates in Baltimore are as high or higher than those reported from previous studies. National projections indicate that greater than 3 million persons are visually impaired, 890,000 of whom are bilaterally blind by US definitions.

Applications of Covariance Structure Modeling in Psychology: Cause for Concern?

Abstract: Methods of covariance structure modeling are frequently applied in psychological research. These methods merge the logic of confirmatory factor analysis, multiple regression, and path analysis within a single data analytic framework. Among the many applications are estimation of disattenuated correlation and regression coefficients, evaluation of multitrait-multimethod matrices, and assessment of hypothesized causal structures. Shortcomings of these methods are commonly acknowledged in the mathematical literature and in textbooks. Nevertheless, serious flaws remain in many published applications. For example, it is rarely noted that the fit of a favored model is identical for a potentially large number of equivalent models. A review of the personality and social psychology literature illustrates the nature of this and other problems in reported applications of covariance structure models.

Predicting Femoral Neck Strength From Bone Mineral Data: A Structural Approach

Abstract: An interactive computer program was developed to derive femoral neck geometry from raw bone mineral image data for an estimate of hip strength using single plane engineering stress analysis. The program, which we call Hip Strength Analysis (HSA), was developed as an attempt to improve the predictive value of hip bone mineral data for osteoporosis fracture risk assessment. We report a series of experiments with an aluminum phantom and with cadaver femora, designed to test the accuracy of derived geometric measurements and strength estimates. Using data acquired with both Lunar DP3 (DPA) and Hologic QDR-1000 (x-ray) scanners, HSA computed femoral neck cross-sectional areas (CSA) and cross-sectional moments of inertia (CSMI) on an aluminum phantom were in excellent agreement with actual values (r greater than .99). Using Lunar DP3 data, CSA and CSMI measurements at mid-femoral necks of 22 cadaver specimens were in good general agreement with literature values. HSA computed cross-sectional properties of three of these specimens were compared with measurements derived from sequential CT cross-sectional images. Discrepancy between the two methods averaged less than 10% along the length of the femoral neck. Finally, breaking strengths of 20 of the femora were measured with a materials testing system, showing better agreement with HSA predicted strength (r = .89, percent standard of the estimate (%SEE) = 21%) than femoral neck bone mineral density (r = .79, %SEE = 28%).

The multiple semantics hypothesis: Multiple confusions?

Abstract: In this paper we discuss the issue of multiple versus unitary semantics. We argue that the notion of multiple semantics (as currently articulated) does not, in fact, represent a theory of semantic organisation but is, instead, an arbitrary conjunction of a set of independent assumptions which are either unmotivated or, if motivated, equally compatible with a unitary semantics hypothesis. Furthermore, the empirical evidence that has been cited as support for this hypothesis is equally compatible with variants of the unitary semantics hypothesis. A model of semantic processing—the Organised Unitary Content Hypothesis (O.U.C.H.)—that is able to account for reported patterns of dissociation of performance is discussed briefly.

Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer. Lung Cancer Study Group.

Abstract: The p53 gene has been implicated as a tumor suppressor gene with mutations found in common human cancers We examined 51 early stage, primary, resected non-small cell lung cancer specimens using an RNAase protection assay and cDNA sequencing Mutations changing the p53 coding sequence were found in 23/51 (45%) tumor specimens, but not in the corresponding normal lung, were distributed between codons 132 to 283, and included tumors with and without 17p allele loss Fifteen of the 23 mutations lay in the predicted binding regions for SV40 large T antigen, and 14 were located in regions highly conserved between species G to T transversions were a common result of p53 mutations in lung cancer compared to other cancers suggesting exposure to different mutagens In univariate and multivariate analysis the presence of p53 mutations was associated with younger age and squamous histology However, the presence of p53 mutations was not significantly associated with tumor stage, nodal status or sex and was found in all histologic types of lung cancer We conclude that somatic mutations in the p53 gene play an important role in the pathogenesis of early stage non-small cell lung cancer