Showing papers by "University of Maryland, Baltimore published in 1983"

New diagnostic criteria for multiple sclerosis: guidelines for research protocols.

Abstract: Several schemes for the diagnosis and clinical classification of multiple sclerosis (MS) have been advanced [l}. The best known is that published by Schumacher et alC31. The criteria for this scheme were established in order to select patients for participation in therapeutic trials, and pertain only to what might be called definite MS. No provision was made for incorporating supportive laboratory data into the diagnostic criteria. As no reliable specific laboratory test for the diagnosis of MS has been discovered, the diagnosis remains a clinical one, and there is still a need for clinical diagnostic criteria. However, several laboratory and clinical procedures have been developed within the last decade which aid greatly in demonstrating neurological dysfunction attributable to lesions, and even the lesions themselves. One problem with the various published diagnostic classifications is their discrepant terminology: what is considered “probable” in one is called “definite” in another. Another problem is that all the proposed schemes require much subjective judgment, a difficulty which cannot be completely overcome but can be diminished by adding to the clinical evaluation the results of laboratory, neuroimaging, neuropsychological, and neurophysiological procedures. Today there is a need for more exact criteria than existed earlier in order to conduct therapeutic trials in multicenter programs, to compare epidemiological surveys, to evaluate new diagnostic procedures, and to estimate the activity of the disease process in MS. Method and Procedure

Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain

Abstract: A current hypothesis links the neuroexcitatory properties of certain acidic amino acids to their ability to cause selective neuronal lesions. Intracerebral injection of the neuroexcitatory tryptophan metabolite, quinolinic acid, has behavioral, neurochemical, and neuropathological consequences reminiscent of those of exogenous excitotoxins, such as kainic and ibotenic acids. Its qualities as a neurotoxic agent suggest that quinolinic acid should be considered as a possible pathogenic factor in neurodegenerative disorders.

Quenching of Fluorescence

Abstract: Fluorescence quenching refers to any process which decreases the fluorescence intensity of a given substance. A variety of processes can result in quenching. These include excited state reactions, energy transfer, complex formation, and collisional quenching. In this chapter we will be concerned primarily with quenching resulting from collisional encounters between the fluorophore and quencher, which is called collisional or dynamic quenching. We will also consider static quenching, which is due to complex formation. Static quenching is a frequent complicating factor in the analysis of dynamic quenching. In addition to the processes described above, apparent quenching can occur due to the optical properties of the sample. For example, high optical densities or turbidity can result in decreased fluorescence intensities. This is a trivial type of quenching which contains little molecular information. Throughout this chapter we will assume such trivial effects are not the cause of the observed decreases in fluorescence intensity.

Ca2+ ions can affect intracellular pH in mammalian cardiac muscle

Abstract: Although intracellular pH (pHi) has important effects on both the mechanical and electrical properties of cardiac muscle1–3, the control of pHi in the heart is still poorly understood. One important determinant of pHi appears to be the transmembrane Na+ gradient4,5. It has therefore been suggested that Na+–H+ exchange assists in the control of pHi in heart as has been proposed for other excitable cells6–8. However, pHi and the intracellular Ca2+ concentration ([Ca2+]i) are interdependent in a variety of tissues9–11 and it has been shown recently that pHi can affect [Ca2+]i in cardiac muscle5,12. As [Ca2+]i in cardiac muscle is also strongly influenced by the transmembrane Na+ gradient5 it is possible that the apparent Na+ -dependence of pHi is secondary to changes in [Ca2+]i. Previous work in cardiac muscle has not been able to separate the effects of Na+–H+ exchange and [Ca2+]i on pHi (refs 4, 5). Here we demonstrate in cardiac muscle that an increase in [Ca2+]i produces an intracellular acidification which cannot be ascribed to Na+–H+ exchange.

Introduction to Fluorescence

Abstract: Luminescences the emission of photons from electronically excited states.. Luminescence is divided into two types, depending upon the nature of the ground and the excited states. In a singlet excited state, the electron in the higher-energy orbital has the opposite spin orientation as the second electron in the lower orbital. These two electrons are said to be paired. In a triplet state these elelectrons are unpaired, that is, their spins have the same orientation. Return to the ground state from an excited singlet state does not require an electron to change its spin orientation. A change in spin orientation is needed for a triplet state to return to the singlet ground state. Fluorescence is the emission which results from the return to the lower orbital of the paired electron. Such transitions are quantum mechanically “allowed” and the emissive rates are typically near 108 sec-1. These high emissive rates result in fluorescence lifetimes near 10-8 sec or 10 nsec. The lifetime is the average period of time a fluorophore remains in the excited state. Phosphorescence is the emission which results from transition between states of different multiplicity, generally a triplet excited state returning to a singlet ground state. Such transitions are not allowed and the emissive rates are slow. Typical phosphorescent lifetimes range from milliseconds to seconds, depending primarily upon the importance of deactivation Processes other than emission. Throughout this book we will be concerned primarily with the more rapid phenomenon of fluorescence.

Cellular calcium fluctuations in mammalian heart: direct evidence from noise analysis of aequorin signals in Purkinje fibers

Abstract: Indirect evidence suggests that fluctuations, or oscillations, in the intracellular free calcium concentration [( Ca2+]i) can occur spontaneously in intact cardiac preparations, but such [Ca2+]i fluctuations have never been demonstrated directly. We used the bioluminescent Ca2+-sensitive protein aequorin to detect fluctuations in the [Ca2+]i in canine cardiac Purkinje fibers. Noise analysis of the aequorin luminescence reveals prominent peaks of power density at frequencies of 1-4 Hz; these peaks become larger and shift to higher frequencies as the [Ca2+]i increases. Caffeine and ryanodine abolish the [Ca2+]i fluctuations, suggesting that Ca2+ release and uptake by the sarcoplasmic reticulum generate these events. When [Ca2+]i fluctuations are present, less tension is produced at any given level of mean aequorin luminescence. Thus, [Ca2+]i fluctuations will undermine attempts to relate [Ca2+]i and force in intact myocardium.

Single sodium channels from rat brain incorporated into planar lipid bilayer membranes

Abstract: A voltage- and time-dependent conductance for sodium ions is responsible for the generation of impulses in most nerve and muscle cells1. Changes in the sodium conductance are produced by the opening and closing of many discrete transmembrane channels2. We present here the first report of electrical recordings from voltage-dependent sodium channels incorporated into planar lipid bilayers. In bilayers with many channels, batrachotoxin3 (BTX) induced a steady-state sodium current that was blocked by saxitoxin4 (STX) at nanomolar concentrations. All channels appeared in the bilayer with their STX blocking sites facing the side of vesicle addition, allowing us to define that as the extracellular side. Current fluctuations due to the opening and closing of single BTX-activated sodium channels were voltage-dependent (unit conductance, 30 pS in 0.5 M NaCl): the channels closed at large hyperpolarizing potentials. Slower fluctuations of the same amplitude, due to the blocking and unblocking of individual channels, were seen after addition of STX. Block of the sodium channels by STX was voltage-dependent, with hyperpolarizing potentials favouring block. The voltage-dependent gating, ionic selectivity and neurotoxin sensitivity suggest that these are the channels that normally underlie the sodium conductance change during the nerve impulse.

Sexual Abuse of Young Children

Abstract: For an 18-month period, all sexual abuse cases were referred to a project social worker. From her initial interview and the medical records, data were analyzed for 113 children who were 12 years of age or younger. It was found that half were five years or younger and three-fourths of the cases were female children. Reasons were discussed as to why females are more likely to be identified as sexually abused cases. A higher than average rate of gonorrhea was found among the pediatric group studied. While only 44 per cent of abusers were relatives of the abused, almost all (93%) were known to the family. If a relative were the alleged abuser, there was a high probability that it was a father, stepfather, or uncle.

Regeneration of hamster tracheal epithelium after mechanical injury. IV. Histochemical, immunocytochemical and ultrastructural studies.

Abstract: All stages of regeneration in hamster tracheal epithelium were studied following a denuding mechanical injury. At 1 h all the cells had sloughed from the wound site leaving a bare and sometimes disrupted basal lamina. Viable cells at the wound margins rapidly changed shape, flattened and migrated to cover the denuded lesion by 12 h. In addition, epithelial cells that remained viable demonstrated sublethal changes that included the rapid discharge of mucous granules from secretory cells, internalization of cilia by ciliated cells and evidence of heterophagy in both cell types. By 24 h a wave of epithelial cell divisions occurred, primarily by secretory cells. This produced a multilayered epidermoid metaplasia that was best developed at 48 h. The metaplastic epithelium was largely composed of cells with both secretory (mucous granules) and epidermoid (tonofilament bundles and numerous desmosomes) characteristics. The peroxidase-antiperoxidase (PAP) method demonstrated a few keratin-positive cells in the wound as early as 12 h post-wounding and keratin was demonstrated in more cells by 24 h. All cells in the metaplastic wound epithelium were keratin-positive by 48 h. Following 48 h some of the most superficial keratinized cells sloughed from the epithelium and the keratin content of the remaining cells began to decline. At 72 h pre-ciliated and pre-secretory cells were seen in the wound. Pre-ciliated cells were characterized by an abundant electron-lucent cytoplasm, large pale nucleus, filiform apical microvilli and evidence of ciliogenesis, similar to that seen during fetal development. Pre-ciliated cells often contained apical mucous granules, apparently carried over from the parent secretory cells. With the appearance of these columnar cells the normal mucociliary morphology was restored in small wounds by 120 h, but some persistent epidermoid metaplasia remained in the large wounds through 168 h post-wounding. These data provide further evidence for the important role of secretory cells in the histogenesis of epidermoid metaplasia and the regeneration of normal morphology following injury. The implications of these findings in understanding the histogenesis of other lesions in the tracheo-bronchial epithelium are discussed.

Instrumentation for Fluorescence Spectroscopy

Abstract: The successful application of fluorescence methods requires an understanding of the instrumentation. Considerable attention to the experimental details is necessary. There are two reasons for this. First, fluorescence is a highly sensitive method. The gain or amplification of the instruments can invariably be increased to obtain observable signals. However, these signals may not originate with the fluorophore of interest. Instead, one may observe interference due to background fluorescence from the solvents, light leaks in the instrumentation, stray light scattered by turbid solutions, Rayleigh and/or Raman scatter, to name a few. Secondly, there is no ideal spectrofluorometer and these instruments do not yield true excitation or emission spectra. This is because of the nonuniform spectral output of the light sources and the wavelength-dependent efficiency of the monochromators and of the photomultiplier tubes. The polarization or anisotropy of the emitted light can also affect the measurement of fluorescence intensities. To obtain reliable spectral data one needs to be aware of and control these numerous factors. In this chapter we will discuss the properties of the individual components in a spectrofluorometer and those properties of samples which affect the measured parameters. In our discussion of these instrumental factors we will stress the acquisition of excitation and emission spectra. However, similar concerns are important in the measurement of fluorescence lifetimes and anisotropics, which will be described in Chapters 3 and 5.

Clinical evaluation of freeze-dried bone allografts in periodontal osseous defects. Part III. Composite freeze-dried bone allografts with and without autogenous bone grafts.

Abstract: Freeze-dried bone allografts (FDBAs) were evaluated alone and in combination with various types of autogenous bone in the treatment of periodontal osseous defects. A total of 381 defects were evaluated by surgical reentry approximately 1 year after grafting. Reentry data were compared with similar data obtained when the grafts were placed. Osseous regeneration and pocket reduction were rated as complete, greater than 50%, less than 50%, or failed. Complete or greater than 50% regeneration was considered successful. When compared with FDBAs, composite freeze-dried bone allografts/autogenous bone grafts (FDBA/ABGs) appear to offer significantly improved results in both osseous regeneration and pocket reduction. Use of composite FDBA/ABGs resulted in significant improvement in the treatment of combination one/two-wall defects and furcation involvements. A trend of improvement was seen with two-wall defects. The surgical data indicated that complete wound closure and the use of antibiotics enhanced graft success. The results also indicated that the presence of endodontically obturated teeth may be a consideration in the success or failure of the graft.

Reliability, validity, and clinical utility of the social functioning exam in the assessment of stroke patients.

Abstract: Social functioning is an important variable in the rehabilitation of stroke patients. We have designed a 28 item semi-structured interview to measure social functioning and have used this instrument in 103 stroke patients in whom we were investigating the occurrence of mood disorders. The social functioning exam was demonstrated to have high interrater and test-retest reliability as well as good agreement with social functioning as measured by other instruments or clinical assessment. The utility of the measurement of social functioning in the assessment of post-stroke mood disorders was demonstrated by the significant correlation between severity of depression and the degree of dysfunction in social functioning six months after the acute stroke, as well as the significant difference in mean social functioning scores between non-depressed and depressed groups.

Summary of a workshop on enteropathogenic Escherichia coli.

Abstract: A workshop on enteropathogenic Escherichia coli (EPEC) was held on September 20th and 21st 1982 at the National Institutes of Health. 50 investigators from 8 countries discussed the epidemiology diagnosis and pathogenesis of EPEC. By consensus of the workshop participants EPEC were defined as diarrheagenic E. coli belonging to serogroups epidemiologically incriminated as pathogens but whose pathogenic mechanisms have not been proven to be related either to heat labile enterotoxins (LT) or heat stable enterotoxins (ST) or to Shigella like invasiveness. EPEC adhere in a seemingly pathognomonic way to the intestinal epithelium. Due to the fact that investigation of EPEC had been minimal for 25 years the workshop was designed to provide new research directions. Participants reevaluated the role of EPEC as human diarrheal agents and identified existing and provocative possibilities for further investigation. Dr. Roy M. Robins-Browne provided a historical overview. Other participants discussed the worldwide magnitude of the problem diagnosis by serotyping mechanisms of pathogenesis mechanisms of pathogenesis animal models for EPEC adhesiveness tissue culture models for EPEC adhesiveness and mechanisms of pathogenesis. Investigators from several developing countries showed EPEC to be the cause of many epidemic and sporadic cases of the infantile diarrhea that occurs mostly in the summer. EPEC appears to have become a less frequent cause of epidemics in both Europe and America. A spectrum of clinical illnesses due to EPEC occurs but diarrhea caused by EPEC is often severe and protracted. Both in vitro and in vivo studies clearly identify a characteristic histopathologic lesion of enteroadhesiveness as manifested by both intestinal brush border destruction and epithelial cell plasma membrane pedestal formation at the sites of EPEC attachment as seen by electron microscopy. Newly developed animal model systems in pigs and rabbits should help elucidate pathogenic mechanisms of EPEC. Recommendations for future investigations include: reinvestigate the epidemiology of EPEC in the 1980s including their geographic distribution seasonability and relative importance in relation to other more recently discovered pathogens; learn the reasons for age related susceptibility to EPEC related diarrhea and why it presents almost exclusively as a disease of infants younger than 2 years of age; develop simplified accurate diagnostic methods including gene probes or antisera to unique pathogenic factors phenotypically expressed and resolve current confusion about the results of different EPEC toxin assays and the characterizations of the toxins themselves.

Microwave Coagulating Scalpel

Abstract: We present an initial report on the design and performance of a device which combines the heating and coagulating effects of a microwave field with the surgical scalpel. The device is intended to control hemorrhage in the surgical treatment of highly vascular organs such as the spleen and liver. Preliminary experiments in splenic surgery using dogs have indicated the utility of this technique.

The influence of patients' age and tumor grade on the prognosis of carcinoma of the cervix

Abstract: Many factors can influence the prognosis of cancer of the cervix. They range from clinical staging, various histologic cell types, to extensions into the endometrium. Very little is known about the influence of the patients- age and constitutional status of the host (patient) on the prognosis of cervical cancer. Over the past several years, we have been observing that when cancer of the cervix occurs in the relatively young patient, they tend to be more aggressive and inspite of the usual accepted treatment, the majority of them do not survive their disease. From 1969 to 1974, 561 patients with proven invasive squamous cell carcinoma of the cervix were treated by irradiation only in the Department of Radiation Therapy, University of Maryland Hospital. Of these, 94 patients were studied and their ages ranged from 23 to 39 years. They were staged following FIGO guidelines and subject to the usual irradiation treatment for cervical cancer. All patients are eligible for a minimum five-year follow-up and the absolute five-year disease-free survival is as follows: Stage I, 70.2%, (33/47); Stage II, 54%, (14/26); Stage III, 17%, (3/18) and Stage IV, 0%, (0/3). One of the most interesting features observed in Stage I and II disease is distant disease; 26% for Stage I and 42% for Stage II. Further analysis of our result for Stage I and II shows that tumor grading may be responsible for poor outcome. Three Grade systems were used for the study and the result clearly shows that Grade III or poorly differentiated squamous cell carcinoma had the poorest five-year survival; for example, survival for Stage I disease is 43% and 44% for Stage II. Analysis of the failures following the treatment suggests that about 50% of patients with Grade III disease have already had distant disease by the time the diagnosis was made. Recommendations for futher appropriate treatment is suggested.

Interstitial microwave hyperthermia for brain tumors. Results of a phase-1 clinical trial.

Abstract: The technical feasibility and clinical safety of interstitial microwave hyperthermia was evaluated in six patients with glioblastoma and malignant astrocytoma. Prior to entry into the study, each patient had received surgery, radiation and nitrosourea chemotherapy. All patients were implanted at open craniotomy with a flexible microwave radiator/sensor (o.d. 1.5 mm) and transcutaneously connected to a 2450 MHz microwave generator. Intraoperative thermal field plots and cooling curves were obtained with the aid of non-perturbing probes (o.d. 1.2 mm) perpendicularly driven into the tumor at fixed radial distances from the central antenna. In comparison to similar measurements carried out in normal feline brains, human gliomas were unable to efficiently dissipate heat as demonstrated by doubling of the effective diameter of the thermal field to 4 cm and by prolongation of the decay time in all cooling curves. Patients were also implanted with subarachnoid ICP monitors over the contralateral hemisphere. Two postoperative treatments were given at 45°C for 60 min on the night of surgery and 48 hr later. No patient was aware of power on/ power off, there were no permanent neurologic sequelae and there were no significant changes in the ICP. Power was manually controlled with visual feedback in the first three patients and automatically controlled by a computer-based system in the final three patients. Four of the six patients have lived 18 months after implantation and two of these have negative CT scans at 18 and 27 months since recurrence. It appears that interstitial microwave hyperthermia is both feasible and safe within the intracranial cavity and that combined interstitial irradiation and hyperthermia deserves clinical study.

Serologic Differentiation Between Antitoxin Responses to Infection with Vibrio cholerae and Enterotoxin-Producing Escherichia coli

Abstract: A ganglioside enzyme-linked immunosorbent assay (ELISA) was used to study and attempt to differentiate between antitoxin responses in persons infected with either Vibrio cholerae or Escherichia coli producing heat-labile enterotoxin. In most cases (69%-94%), experimentally infected North Americans and naturally infected Bangladeshis responded to either infection with significant (greater than twofold) increases in serum antibody titer to both heat-labile enterotoxin and cholera toxin. In all but one instance, the response was higher to the homologous than to the heterologous toxin, and for the Americans the homologous antitoxin titers remained significantly higher for at least one year. Determination of levels of antibodies to purified subunits A and B of cholera toxin by an ELISA showed that V. cholerae infection in most instances induced a significant response to subunit B but rarely to subunit A. E. coli infection, on the other hand, induced only slight increases in antibody titer to either subunit.

Determination of Sex With a Discriminant Analysis of New Pelvic Bone Measurements: Part II

Abstract: The pelves of 100 black skeletons were measured on both sides for the following: (1) length from the superiormost aspect of the pubic symphysis to the nearest rim of the acetabulum (PS-A), (2) length from the highest point of the pubic tubercle to the nearest rim of the acetabulum (PT-A), (3) acetabular diameter (AD), (4) the vertical distance from the anterior aspect of the ischial tuberosity to the farthest rim of the acetabulum (IT-A), and (5) greatest femur head diameter. From these, three indices were derived: AD/PS-A (acetabulum/pubis index), AD/PT-A (acetabular diameter/pubic tubercle-acetabular rim index), and IT-A/PS-A (ischium-acetabulum height/pubic symphysis-acetabular rim index). The left AD/PS-A ratio and left IT-A height proved statistically to be of greatest discriminating value. Using these two variables, a discriminant function was derived which, followed by sorting with femur head diameter, accurately classified 97% of our sample. The acetabulum/pubis index alone with subsequent sorting by femur head diameter correctly assigned 96% of our sample. While this does not represent an improvement of predicatability over similar methods using the ischium/pubis index, measurements required for the acetabulum/pubis index are more easily defined and should, therefore, reduce the chance of observer error.

11 Positive Slow Wave and P300: Association and Disassociation

Abstract: Publisher Summary Slow Wave and P3b are members of a group of long latency, positive polarity, and endogenous event-related potential (ERP) components now known as the late positive complex (LPC). In the earliest experiments in which Slow Wave was found, it appeared that Slow Wave related to experimental variables in much the same manner as did P3b. As a result, during the early period there was little focus on Slow Wave. However, in recent years evidence for a behavioral dissociation between Slow Wave and P3b has been accumulating. The purpose of this chapter is, to review and attempt to evaluate the similarities and differences between Slow Wave and P3b. The initial reports of LPC activity described a single prominent component with a peak latency of about 300 msec. It was referred to as the late positive component or P3 or P300. Subsequent experiments established that P300 amplitude is generally largest over parietal scalp. P300 potentials have generally been elicited by events that are made relevant by serving various purposes: (1) to provide a subject with feedback information concerning the outcome of a prior task; (2) to be the object of a discrimination or counting task; (3) to be an imperative signal requiring performance of a motor response.

The mandibular corpus of female primates: taxonomic, dietary, and allometric correlates of interspecific variations in size and shape.

Abstract: Measurements were taken on skulls of 253 adult female anthropoid primates from 32 species, in order to determine patterns and possible causes for variation among species in the cross-sectional size and shape of the mandibular corpus under M1. When all 32 species are considered as a group, there is a tendency for corpus shape to become more robust with increasing body size. However, this does not hold for colobines or cercopithecines evaluated separately. When diets are classified into the general categories of folivory or frugivory, neither size-adjusted measurements of mandibular corpus breadth and height, nor estimates of the second moments of inertia or the polar moment of inertia of the mandibular cross section, show any relationship to dietary variation among species. Species reported to include hard nuts in their diets have larger mandibular cross sections than other species, and the size of the corpus is significantly correlated with size of the dentition and molar enamel thickness. A biomechanical model taking into account frictional effects of tooth-to-tooth contact indicates that mandibular corpus robusticity may not be related to a large horizontal component of force during mastication.