Showing papers by "Georgetown University published in 1982"

Substantia nigra: site of anticonvulsant activity mediated by gamma-aminobutyric acid.

Abstract: Localization of the anatomic substrate for anticonvulsant activity mediated by gamma-aminobutyric acid (GABA) was examined using intracerebral injections of GABA agonists. Blockade of tonic hindlimb extension in the maximal electroshock test and blockade of tonic and clonic seizures produced by pentylenetetrazole and bicuculline were obtained by elevating GABA in the ventral midbrain tegmentum. Elevation of GABA in forebrain and hindbrain areas had no effect on convulsant activity. Blockade of tonic and clonic seizures was also obtained after microinjections of the direct GABA receptor agonist, muscimol, into the midbrain. The substantia nigra was identified as the critical midbrain site for GABA-mediated anticonvulsant activity. Local injection of GABA agonists into the midbrain provided seizure protection without a widespread augmentation of GABA-mediated activity throughout the brain and without impairing either alertness or motor function. Synapses in the substantia nigra appear to represent an important control mechanism for inhibiting the propagation of generalized convulsions.

International Interest Rate and Price Level Linkages under Flexible Exchange Rates: A Review of Recent Evidence

Abstract: In an open economy, the scope for activist stabilization policy depends on the nature of the lincages between domestic and international markets for goods and assets. Tgo important relationships--purchasing power parity and uncovered interest-rate parity--have received extensive empirical atpention in recent years and are fundamental building blocks of several eipirical ex- change rate models. This paper reviews and extends recent econometric findings on these two classical parity relationships and on their corollary, the international equality of expected real interest rates. Econometric tests assuming rationality of expectations are on the whole unfavorable to the classical parity relationships: with few exceptions, they are strongly rejected. A central theme in the review of empirical work is the conditional heteroskedasticity of inflation and exchange rate forecast errors and the bias this statistical problem may impart to tests of inter- national parity relationships. The paper proposes and implements a test for conditional heteroskedasticity which in many cases produces strong evidence that the problem is indeed important.Institutional subscribers to the NBER working paper series, and residents of developing countries may download this paper without additional charge at www.nber.org.

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.

Adhesive Bonding of Various Materials to Hard Tooth Tissues: Improvement in Bond Strength to Dentin

Abstract: Used in sequence, solutions of an acidic mordant, a surface-active comonomer, and a coupling agent having methacrylate and aromatic carboxyl groups were used to prepare dentin surfaces in vitro for strong bonding with a composite resin.

Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well‐differentiated carcinoma

Abstract: Endometrial curettings from 204 patients containing severe forms of atypical hyperplasia, carcinoma in situ, and well-differentiated carcinoma were compared with subsequent hysterectomy specimens to evaluate and identify the most useful histologic criteria for predicting the presence of invasive carcinoma. Endometrial stromal invasion, increased degrees of nuclear atypism, mitotic activity, cellular stratification, and epithelial necrosis in curettings were associated with a greater likelihood of carcinoma in the uterus. Of these, stromal invasion was the most significant feature. When stromal invasion was absent, carcinoma was present in the uterus in only 17%, and the carcinomas were well differentiated and confined to the endometrium or only superficially invasive. When stromal invasion was present in curettings, residual carcinoma was present in the uterus in half, and of these, one third were moderately or poorly undifferentiated and a quarter invaded deeply into the myometrium. The criteria for invasion are 1) an irregular infiltration of glands associated with an altered fibroblastic stroma or desmoplastic response; 2) a confluent glandular pattern in which individual glands are uninterrupted by stroma and merge to form a cribriform pattern of stromal replacement; 3) an extensive papillary pattern; and 4) replacement of stroma by masses of squamous epithelium. To qualify as invasion, 2, 3, and 4 must occupy at least one half (2.1 mm) of low power field 4.2 mm in diameter. Because of the important role of stromal invasion in predicting prognosis, future classifications of endometrial neoplasia should utilize this feature in distinguishing atypical hyperplasia from well differentiated adenocarcinoma.

Human T-cell clones recognize chemically synthesized peptides of influenza haemagglutinin

Abstract: The continual variation in the antigenic structure of the haemagglutinin (HA) molecule is associated with the appearance of new epidemics or pandemics of influenza in immune populations1. The detailed analysis of HA structure has provided the molecular basis of this phenomenon2–4 and while four antibody-binding sites have been suggested4, the epitopes of HA that are recognized by T cells remain undefined. Using chemically synthesized peptides corresponding to sequences of the HA molecule5, we have investigated the antigenic determinants recognized by long-term T-lymphocyte lines and clones induced with HA and maintained in T-cell growth factor (TCGF or interleukin-2, IL-2). The data suggest that HA-specific T-cell populations contain the repertoire to respond to all the synthetic peptides analysed. However, when responses are analysed at the clonal level, one peptide located at the carboxy-terminus of the HA1 molecule and discrete from the proposed antibody-binding sites4 seems to be immunodominant.

A comparison of combination chemotherapy and combined modality therapy for locally advanced gastric carcinoma

Abstract: This controlled trial compared the survival of 90 patients with locally advanced gastric carcinoma treated with either chemotherapy alone (5-FU and methyl-CCNU) or external radiotherapy of 5000 rad combined with the same chemotherapy. The minimum period of followup is 4 years. During the initial 12 months, combined modality therapy was associated with an increased number of early deaths attributable to progression of tumor within the radiation field, or nutritional and hematologic complications. During the second to fourth years of followup, patients treated with combined radiation therapy have shown a significantly lower death rate compared to those treated with chemotherapy alone, with eight of 45 patients alive and disease-free. Patients who received only chemotherapy, in contrast, have demonstrated a continued probability for tumor relapse and death, with three of 45 patients alive at 4 years. Palliative resection of the primary tumor was associated with an improved survival, independent of the form of postoperative therapy employed. It is possible that the superior late survival achieved with combined modality therapy in this program can be further improved with measures to decrease the toxicity of upper abdominal irradiation, and with the use of more effective forms of chemotherapy.

The Morphology and Evolution of the Ear in Actinopterygian Fishes

Abstract: SYNOPSIS. In this paper we consider various aspects of the anatomy and ultrastructure of the actinopterygian ear and make a number of suggestions on the possible adaptive significance of the structural specializations. The focus of the arguments is based upon the substantial inter-specific variation in teleost auditory systems as measured anatomically, behaviorally, and physiologically. It is potentially of considerable significance that the major points of inter-specific variation in the teleost ear are associated with the gross morphology and ultrastructure of the otolithic organ most often implicated in sound detection, the sacculus. Analysis of patterns of sacculus ultrastructure has led to the conclusion that there are, in effect, only about five different saccular ultrastructural patterns but that these patterns are broadly found throughout the teleost fishes. Based upon patterns of inter-specific variation in the sacculus and in other aspects of the ear and more peripheral auditory structures ( e.g. , swimbladder), it is argued that adaptations encountered in the teleost auditory system cannot be used as reliable taxonomic indicators among fishes. Rather, it is proposed that the teleost auditory system is quite maleable in the evolutionary sense, and that interspecific similarities in many features of the auditory system reflect convergent evoluuon, rather than phylogenetic affinities. The actual selective pressures operating in the evoluuon of the fish auditory system are still essentially unknown. In addition, we cannot be certain that similar ear patterns in different species reflect convergent evolution (or common ancestry), or that conversely, different ear patterns among species reflect differences in auditory function.

Local cerebral glucose utilization in non-rapid eye movement sleep

Abstract: Sleep is accompanied by alterations in neurophysiological activity in many discrete regions in the brain1. Such alterations could be expected to be accompanied by corresponding changes in local metabolic rate2. We have now looked for the specific regions involved in sleep, at least in the stages other than rapid eye movement (REM) sleep, by using the [2-14C]deoxyglucose method for measuring local cerebral glucose utilization3 in the rhesus monkey. Contrary to what many have predicted, animals during stages 2–4 of sleep exhibited a non-selective, generalized 30% decrease in cerebral metabolic rate. Of the 75 structures measured, none exhibited a higher rate in non-REM sleep than in wakefulness.

Antigen-specific human T lymphocyte clones: induction, antigen specificity, and MHC restriction of influenza virus-immune clones.

Abstract: Human peripheral blood lymphocytes from an HLA-Dw1,3 individual were primed in vitro with influenza A virus (A/Texas/1-77/x-49) and subsequently cloned by limiting dilution in TCGF. Of the 96 TLCs originally obtained, nine were characterized in detail. TLCs were antigen specific, responding to influenza A virus, not to influenza B, TGAL, GAT, tetanus toxoid, or KLH, and only when antigen was presented by cells unable to form rosettes with AET-treated SRBC. Presentation of antigen by unseparated PBL often resulted in significant "back stimulation," probably via production of growth factors. The MHC requirements for the induction of TLC proliferation were analyzed. Of four representative clones analyzed, three required Dw1;DR1 compatibility for successful presentation of viral antigens by a panel of antigen-presenting cells. In contrast, one TLC showed an unusual pattern of response that could not be correlated to a particular HLA haplotype. Monoclonal anti-T cell antibody analysis of the surface phenotype of two TLCs maintained in continuous culture for 5 mo indicated that they were OKT3+, 4+, and 8-, consistent with an inducer/helper phenotype. To confirm the clonal nature of TLCs, data on the functional properties of TLC subclones are also presented.

A human suppressor T cell clone which recognizes an autologous helper T cell clone

Abstract: In contrast to the many reports of IL-2 dependent proliferating, helper or killer cell clones1, there is only a single report of an IL-2 dependent suppressor cell clone2, in the mouse. However by the same cloning procedures used to generate human helper cells3, suppressor cell clones to influenza virus could not be generated, and so another strategy was used. Jerne's network hypothesis4 proposes that immune regulation results from lymphoid cell receptors recognizing determinants on other lymphoid cell receptors. If this is the case it should be possible to generate regulatory T cell clones against other T cells and we report here the generation of an autologous suppressor cell clone which recognizes and inhibits the function of a human helper T cell clone. Such an autologous suppressor cell clone provides a new approach to understanding the pathways and molecular events involved in immune regulation. Mutual stimulation of the suppressor cell clone and the target helper cell clone in the absence of back stimulation, provides direct experimental evidence for the existence of interactions between T cell receptors, and thus suggests that the specificity of the suppressor cell clone is for the antigen receptor of the helper cell.

Nucleotide sequence of the transforming gene of avian myeloblastosis virus

Abstract: Avian myeloblastosis virus is defective in reproductive capacity, requiring a helper virus to provide the viral proteins essential for synthesis of new infectious virus This virus arose by recombination of the nondefective helper virus and host cellular sequences present within the normal avian genome These latter sequences are essential for leukemogenic activity The complete nucleotide sequence of this region is reported Within the acquired cellular sequences there is an open reading frame of 795 nucleotides starting with the initiation codon ATG (adenine, thymine, guanine) and terminating with the triplet TAG This open reading frame could code for the putative transforming protein of 265 amino acids with a molecular weight of approximately 30,000

Frequency and distribution of papillomavirus structural antigens in verrucae, multiple papillomas, and condylomata of the oral cavity.

Abstract: Sixty-seven proliferous squamous epithelial lesions of the oral cavity were examined for the presence of human papillomavirus whole (structural) virion antigens by a peroxidase-antiperoxidase technique having immunospecificity against genus-specific (common) antigens of the papillomaviruses. A positive reaction for papillomavirus genus specific antigens was found in 18 of 29 verrucae, 2 of 5 multiple papillomas, and 3 of 5 condylomata; common antigens were not detected in 28 keratoacanthomas. The positive reaction was invariably intranuclear in cells having a focal or diffuse distribution in the superficial epithelium. This study shows that a variety of squamous epithelial lesions of the mucosa are associated with human papillomaviruses and suggests that these viruses may play an important role in the etiology of some cases of squamous hyperplasia of the oral cavity.

In vitro influenza virus-specific antibody production in man: antigen-specific and HLA-restricted induction of helper activity mediated by cloned human T lymphocytes.

Abstract: Cloned human T lymphocytes induced with influenza A virus (A/Texas/1/77) and maintained in continuous culture with T cell growth factor were assayed for helper function in the in vitro production of anti-influenza antibody. Helper function mediated by both cloned helper T cells and normal peripheral blood lymphocytes was highly antigen dose-dependent, requiring lower concentrations than that necessary to induce blastogenesis. Optimal help was observed with 1 X 10(2) cloned T cells per culture, whereas excess helper cells inhibited the response. After culture with influenza A virus-induced cloned helper T cells, the antibodies formed were directed against influenza A and not B virus. Furthermore, the cloned helper T cells despite being specific for matrix protein collaborated in the production of predominantly anti-hemagglutinin antibody, suggesting associative recognition of the two discrete antigens. Cellular interactions between cloned helper cells from an HLA-Dw1,3 DR1,3 individual and erythrocyte rosette-negative cells required HLA-Dw1; DR1 compatibility for the production of specific antibody. This was confirmed by using subclones. Finally, it was observed that supernatants of the cloned helper T cells contained functional activity capable of replacing the parent cells in the production of anti-influenza A virus antibody.

Transformation-dependent loss of the hyaluronate-containing coats of cultured cells.

Abstract: The sizes of hyaluronate-containing coats on the surfaces of parent and virus-transformed cell lines (3T3 vs. SV-3T3; BHK vs. PY-BHK) were compared according to the method of Clarris and Fraser (1968, Exp. Cell Res., 49: 181-193) in which fixed red blood cells were allowed to settle slowly on the surface of culture dishes containing the cells. The coats were seen as areas devoid of red blood cells surrounding each of the cultured cells and could be destroyed by the addition of small amounts of streptomyces hyaluronidase, an enzyme specific for hyaluronate. In the case of the parent cell lines (3T3 and BHK), the coats were clearly visible, whereas for their virus-transformed counterparts (SV-3T3 and PY-BHK), the coats were either greatly reduced or absent. To confirm these observations, the amount of hyaluronate associated with each of the cell lines was measured using a direct chemical assay and shown to be significantly greater for the parent cell lines than for their virus-transformed counterparts. In addition, the parent cell lines secreted greater amounts of hyaluronate into the medium and retained a larger fraction of the total amount of hyaluronate at the cell surface than the virus-transformed cells. Thus the larger amount of hyaluronate on the surfaces of the parent cell types may be the result of both a faster rate of production and a decreased rate of release.

A Causal Theory of Enjoyment

Abstract: I shall present a theory of enjoyment, in the form of a definition. The basic idea is that an object of enjoyment causes the subject to experience pleasure by causing occurrent beliefs which satisfy desires concerning the experience itself. Pleasure is identified with occurrent happiness, which can be defined in terms of belief, desire, and thought. I also define degree of enjoyment, as that part of the subject's pleasure attributable to the object of enjoyment. Degree of belief and desire are the fundamental quantities. Finally, I briefly treat negative enjoyment.1

Local cerebral glucose utilization in the newborn macaque monkey

Abstract: The [14C]deoxyglucose method for quantitative determination of local cerebral glucose utilization was employed in newborn macaque monkeys. Values ranged from a high of 180 mumol/100 gm/min in the inferior colliculus to a low of 14 mumol/100 gm/min in the centrum ovale, a wider range than had been found in this laboratory for pubescent monkeys. Relatively low values in white matter overlapped with the generally higher values in gray matter. Rates for structures in the lower neuraxis were equal to or exceeded those reported for the mature animal, while those above the midbrain were generally lower. The auditory system was unique in having rates equal to, or exceeding, its mature levels in all parts of the pathway including the cortex. In the visual system, subcortical structures were at their mature levels while rates in the cortical areas were variably low; nevertheless, the striate cortex had differential rates marking the various laminae. It was possible to demonstrate the metabolic counterpart of the ocular dominance columns in two newborn animals that had had one eye occluded during the experiment. Rates for white matter were above their mature levels, with the differences being greatest in the brainstem and cerebellum. A high correlation between glucose utilization and local blood flow measured with [14C]antipyrine (r = 0.92) was found.

The delivery of bad news in organizations

Abstract: The delivery of bad news is at the center of many organizational processes. Despite the variety of organizational processes involving the delivery of bad news, there is no integrative framework that guides its study. Based on a literature review of professionals who deliver bad news as part of their occupations, this article presents a framework that conceptualizes the delivery of bad news as a process involving a variety of activities in three different, but interrelated, phases—preparation, delivery, and transition. This three-phase model is the guiding framework for the literature review. The article identifies the strategic functions served by different bad news management activities and highlights many dilemmas facing managers in the delivery of bad news. The article concludes with identifying new directions for research on the delivery of bad news in organizations.

Antigen-specific human T lymphocyte clones: Viral antigen specificity of influenza virus-immune clones

Abstract: Human T lymphocyte clones (TLC) specific for type A (A/Texas/1/77) influenza virus and maintained in continuous culture with T cell growth factor, were analyzed to define the cellular specificity pattern of virus recognition. A panel of TLC were stimulated with strains of serologically characterized type A influenza subtypes. Five TLC recognized all the viral subtypes; the remaining clones recognized only subtypes that shared serologically defined determinants with the immunizing subtype. In addition, the 11 TLC were analyzed for their fine antigenic specificity by using the purified viral components hemagglutinin (HA), neuraminidase (NA), matrix protein (MP), and nucleoprotein (NP). Five TLC proliferated in response to NA, four to MP, one to HA, and one to NP. None of the clones responded to the unrelated B strain influenza virus, B/Singapore. Furthermore, the fine specificity of an MP-reactive TLC was confirmed by subcloning.

Partial purification and characterization of particulate acid phosphatase of Leishmania donovani promastigotes

Abstract: 1. More than 90% of the total acid phosphatase activity in a sonicate of L. donovani promastigotes is contained in a particulate fraction (200,000 X g 30 min). The enzyme can be quantitatively extracted and solubilized with the aid of Triton X-100 (0.2 g/100 ml) and purified over 200-fold with 54% yield by chromatography on DEAE-Sephadex, QAE-Sephadex, Sepharose 4B and concanavalin-A Sepharose. 2. The phosphatase is a true acid hydrolase (pH optimum, 5.0-5.5) and has a rather broad substrate specificity; it will catalyze the hydrolysis of 4-methylumbelliferylphosphate, thymolphthalein diphosphate, pyridoxal phosphate, fructose 1,6-diphosphate, glucose 6-phosphate, glucose 1-phosphate, ADP and AMP. 3. It is a large (170,000 daltons in the presence of Triton X-100), stable and acidic enzyme (pI = 4.1) that has the electrophoretic mobility of a type zero or type 1 isoenzyme in acid (pH 4.3) polyacrylamide gels. 4. The enzyme is inhibited by sodium fluoride, 2-mercaptoethanol and mumolar amounts of a number of polyanionic molybdenum and heavy metal complexes that include the following: [C(NH2)3]4[(C3H7O3PO3)2Mo5O15] X 3H2O, [C(NH2)3]2[(C6H5)2AsMo4O15H] X H2O, (NH4)4[SiMo12O40] X H2O and (NH4)6[P2Mo18O62] X 9H2O. 5. L. donovani promastigotes contain very low levels of 10 other acid pH optimum hydrolytic enzymes, with the exception of modest levels of alpha-fucosidase.

Stress-induced plasma beta-endorphin immunoreactivity may predict postoperative morphine usage

Abstract: The relationship between stress and human behavior is studied using general surgery as a stress paradigm. As indices of arousal, presurgery and surgery plasma β-endorphin and cortisol immunoreactivity are assessed. Behavioral analysis is restricted to the measurement of total morphine usage during the first 24 postoperative hours under standard PRN (as needed) clinical orders. Individual patient morphine requirements vary widely (12–56 mg). Both presurgery and mean surgery plasma β-endorphin levels significantly predict morphine requirement, and similar, although not so strong, correlations are found for cortisol. Patient age is also found to be negatively correlated with morphine requirement. When multiple regression analysis is used, the variables of plasma β-endorphin and age predict 70% of the variance in individual morphine requirements.

Choroidal Blood Flow: II. Reflexive Control in the Monkey

Abstract: Temperature measurements were taken from (1) the retina-choroid in the macula, (2) the scleral surface, or (3) the bulbar conjunctiva of the cynomolgus monkey, while the fellow eye was exposed to a moderate-intensity light source. Light stimulation produced an increase in tissue temperature in the non-light-stimulated eye. The increase in tissue temperature presumably results from a reflexive increase in choroidal blood flow. Hydrogen washout measurements of blood flow in the retina-choroid confirmed this increase in flow. This active mechanism, along with the passive ability of the choroidal circulation to dissipate light-generated heat, may be an important physiologic safeguard in helping to maintain a stable temperature environment for the outer retinal layers in the macula.