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Biomedical subjects

M A Epstein

Publications and source records attributed to M A Epstein.

At least 109 records · Page 6Linked to original sources

Observations on the EB virus envelope and virus-determined membrane antigen (MA) polypeptides.

Experiments have been carried out to identify the polypeptide components of the Epstein-Barr (EB) virus-determined membrane antigen (MA) complex. Cells were radioiodinated using lactoperoxidase and the 125I-labelled surface antigens, released by Triton X100, were analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) after complexing either with human sera having anti-MA activity or with a rabbit antiserum to EB virus. Using cells carrying EB virus isolated from four different conditions, including for the first time nasopharyngeal carcinoma (NPC), we have demonstrated four major polypeptides. One, with a molecular weight of 85,000, was remarkedly constant irrespective of the cell line from which it came; two, with molecular weights varying from 240,000 to 270,000 and from 320,000 to 340,000, showed minor differences in mobility apparently depending on the species of origin of the cells (human or marmoset), rather than disparity between strains of virus. A fourth component, of 160,000 daltons, was found on only two of the cell lines studied. In addition, it has been shown for the first time that the same polypeptides composing the MA complex are present on the viral envelope itself. The fact that the rabbit antiserum to EV virus recognized only the two highest molecular weight MA components, yet showed virus-neutralizing activity, indicates the importance of these two polypeptides for use in a vaccine designed to induce virus-neutralizing antibodies.

Animals↗

Determinants of distortions in CO2 catheter sampling systems: a mathematical model.

A mathematical model was developed to predict the distortions in the measured expiratory CO2 concentration time profile caused by catheter sampling systems. Parameters considered included the expiratory flow and concentration profiles, the sample flow rate, the sample tube dimensions and the sample cell volume. Unless care is taken in choosing the parameters of a catheter sampling system, particularly in the presence of low expiratory flow rates and short expiratory times, the CO2 concentration profile may be severely distorted. In worst case situations end tidal CO2 plateaux may not be recognized or alternately artifactual plateaux may be produced. Sample flow rate and sample cell volume are the most important parameters while distortion within the sample tube itself is relatively less important.

Carbon Dioxide↗

Heart rate and heart rate variability during sleep in aborted sudden infant death syndrome.

Heart rate and heart rate variability were studied during sleep at monthly intervals in 18 normal infants and 12 infants with aborted sudden infant death syndrome during the first four months of life. At each age studied and in both REM and quiet sleep, the aborted SIDS infants had a 5 to 10% faster heart rate. Moreover, the aborted SIDS infants had a 10 to 45% smaller beat-to-beat and overall heart rate variability. Although the differences in overall variability persisted after normalization by the absolute heart rate, the differences in the beat-to-beat variability narrowed. These findings, when taken in conjunction with our previous observation that aborted SIDS infants have a smaller QT index than normal infants, suggest that infants with aborted SIDS have an increase in sympathetic activity or in circulating levels of catecholamines.

Female↗

Spontaneous carotid artery dissection in a 38-year-old man.

Dissection of the left internal carotid artery apparently occurred in a 38-year-old man when he bent over to wash his feet in the shower. Narrowing was demonstrated on a left internal carotid arteriogram. He was treated conservatively, with prophylactic anticoagulation, antihypertensive drug therapy, and weight reduction. He returned to full activity, and after four months the caliber of the narrowed segment was seen to be almost normal on arteriography.

Adult↗

The prevalence of naturally occurring antibodies to human syncytial virus in East African populations.

A seroepidemiological study of naturally occurring antibodies to the human syncytial virus has been carried out by means of an indirect immunofluorescence test on 639 East Africans, consisting of 493 normal Ugandans, 66 Kenyan patients with nasopharyngeal carcinoma (NPC), and 80 Kenyan and Tanzanian patients with various other tumours or non-cancerous conditions. It was found that 3.4% of the normal individuals had antibodies to the virus and serial serum samples were available from 14 of these, permitting the study of antibody class in seroconversion and antibody persistence. As in an earlier survey, a significantly higher incidence of antibodies was found amongst NPC patients. Blocking and indirect immunofluorescence test with simian foamy viruses (SFV) showed some cross-reactivity between SFV 6 and the human syncytial virus, but not identity. The results are discussed in relation to the very real occurrence of natural infection by human syncytial virus in certain geographical regions.

Adolescent↗

Comparison of Epstein-Barr virus strains of different origin by analysis of the viral DNAs.

Epstein-Barr virus (EBV) originating from Burkitt's lymphoma (P3HR-1 and CC34-5), nasopharyngeal carcinoma (M-ABA), transfusion mononucleosis (B95-8), and a patient with acute myeloblastic leukemia (QIMR-WIL) was isolated from virus-carrying lymphoid cell lines after induction with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. Viral DNA was analyzed by partial denaturation mapping and by use of the restriction endonucleases EcoRI, HindIII, and SalI and separation of fragments in 0.4% agarose. By using the restriction enzyme data of B95-8 (EBV) and W91 (EBV) obtained by Given and Kieff (D. Given and E. Kieff, J. Virol. 28:524-542, 1978), maps were established for the other virus strains. Comigrating fragments were assumed to be identical or closely related among the different strains. Fragments of different strains migrating differently were isolated, purified, radioactively labeled, and mapped by hybridization against blots of separated viral fragments. The results were as follows. (i) All strains studied were closely related. (ii) The number of internal repeats was variable among and within viral strains. (iii) B95-8 (EBV) was the only strain with a large deletion of about 12,000 base pairs at the right-hand side of the molecule. At the same site, small deletions of about 400 to 500 base pairs were observed in P3HR-1 (EBV) and M-ABA (EBV) DNA. (iv) P3HR-1 (EBV), the only nontransforming EBV strain, had a deletion of about 3,000 to 4,000 base pairs in the long unique region adjacent to the internal repeats carrying a HindIII site. (v) Small inserted sequences of 150 to 400 base pairs were observed in M-ABA (EBV) and B95-8 (EBV) at identical sites in the middle of the long unique region. (vi) Near this site, an insertion of about 1,000 base pairs was found in P3HR-1 (EBV) DNA. (vii) The cleavage patterns of P3HR-1 virus DNA and the results of blot hybridizations with P3HR-1 virus fragments are not conclusive and point to the possibility that in addition to the normal cleavage pattern some viral sequences may be arranged differently. Even though it is possible that small differences in the genome organization may have significant biological effects, the great similarity among different EBV strains does not favor the hypothesis that disease-specific subtypes exist.

Base Sequence↗

CO2-induced changes in ventilation and ventilatory pattern in normal sleeping infants.

The effect of CO2 on the ventilatory pattern of 18 normal infants was studied during sleep at monthly intervals through the age of 4 mo. Using the barometric method, we measured tidal volume (VT), respiratory cycle time (Ttot), inspiratory time (TI), and expiratory time (TE). Two percent CO2 produced no change in TI and a significant increase in VT and mean inspiratory flow (VT/TI). There was no consistent change in TE or Ttot in either sleep state at any age. The percent increase from base line in instantaneous minute ventilation (VT/Ttot) during REM sleep was similar to that during quiet sleep. We conclude that with inhalation of 2% CO2 in the first 4 mo of life 1) the increase in VT/Ttot results solely from an increase in VT and the percent increase in VT/Ttot is the same in both sleep states and 2) the reflex termination of inspiration by inflation does not play an important role in eupnea during sleep because the increase in VT is not associated with a decrease in TI.

Aging↗

Practical implementation of the barometric method for measurement of tidal volume.

The barometric method is unique in permitting measurement of tidal volume in a totally noninvasive manner. Its application and accuracy have been limited by several complex problems. These include control of inspired gas composition, base-line stability, and asymmetry of processes occurring during inspiration and expiration. A new method is described that addresses these problems and facilitates long-term measurements. New calculations, which avoid previous errors that caused the method to systematically underestimate tidal volume, are illustrated.

Animals↗

Relation of beat-to-beat variability to heart rate in normal sleeping infants.

The relationship of beat-to-beat heart rate variability (delta RR) and instantaneous heart rate was studied in eight normal infants while asleep during the first four months of life. The sleep state (REM or quiet) was determined using neurophysiologic and behavioral criteria. The results of regression analyses indicated that the delta RR values were positively correlated with the instantaneous heart rate (RR intervals). The correlation coefficient range was 0.49 to 0.92 in quiet sleep and 0.50 to 0.93 in REM sleep. Regression analyses supported a linear approximation of the delta RR to RR relation over the RR range investigated (400 to 520 msec). The median slope was 0.124 in REM and 0.117 in quiet sleep. The slopes of these linear functions were similar in both sleep states and at all ages. If beat-to-beat variability is to be used as an index of the integrity of the autonomic nervous system, these results suggest that delta RR be corrected for RR. A model is presented which relates the demonstrated positive correlation of delta RR to RR with the physiology of cardiac output control.

Autonomic Nervous System↗

The R-R interval and R-R variability in normal infants during sleep.

Eighteen normal infants were studied in the first 2 wk of life during sleep and subsequently at their monthly birthdays for the first 4 months of life. The R-R interval was measured with an accuracy of 0.2 msec. Sleep staging was performed visually using electroencephalogram, electrooculogram, and electromyogram, and behaviroal criteria. Our results show that the R-R interval and the beat-to-beat variability are, in general, smaller in rapid eye movement than in quiet sleep. The two sleep states, however, are best differentiated by the overall variability which is characteristically higher in rapid eye movement sleep. The R-R interval as well as the overall and the beat-to-beat variability show minimal values at 1 month and maximal rates of increase between 2 and 3 months of age, indicating that the R-R interval and R-R variability are not simple linear functions of age.

Age Factors↗

Biological and biochemical observations on isolates of EB virus from the malignant epithelial cells of two nasopharyngeal carcinomas.

Foetal, adult seronegative, and cotton-top marmoset lymphocytes have been transformed into cell lines by EB virus from the malignant epithelial cells of two nasopharyngeal carcinomas. The nature of the cell lines was checked by karyotyping and by light and electron microscopy, and the presence of the EB virus genome was demonstrated by immunofluorescence tests. Immunofluorescence also showed the incidence of EB virus-producing cells in each line and this was checked by electron microscopy and the use of a lymphocyte transformation assay. Two foetal-derived lines did not produce virus spontaneously, could not be activated with various inducers, and were found by DNA reassociation kinetics to carry only small numbers of genome copies per cell. An adult-derived line produced virus, could be activated to produce more, and provided enough infectivity to transform marmoset cells. The resulting marmoset line made profuse transforming virus; it thus provides the first abundant source of NPC-derived infectious EB virus for comparative studies. The results are discussed in relation to the interactions with comparable target cells of EB virus from normal individuals and from patients with other diseases.

Animals↗

Identification of murine endogenous xenotropic retrovirus in cultured multicellular tumour spheroids from nude-mouse-passaged nasopharyngeal carcinoma.

After nude-mouse-passage, a carcinoma of the nasopharynx was found to contain a few scattered C-type retrovirus particles. Culture of this nude-mouse-grown material over solid agar allowed the human tumour cells to grow as multicellular spheroids which increased in number by budding and could be subcultured for up to 6 months. Within the spheroids the human tumour cells expressed increased retrovirus replication and large numbers of C-type particles were observed. Treatment with a halogenated pyrimidine further enhanced the virus production. This tissue culture system provided sufficient virus production for the identification of the retrovirus as an endogenous xenotropic murine leukaemia virus and not a human agent.

Animals↗

High-resolution determination of the R-R interval.

A preprocessor is described that determines the time interval between successive R waves of the electrocardiogram with an error of less than 0.2 ms. It accomplishes this by sepearting in hardware the function of determining the approximate location of the R wave from the function of localizing with great accuracy the peak of the wave form. With this device it is possible to detect abnormal heart rate patterns characterized by exceedingly small beat-to-beat variability. The approach may be useful for other bioelectric signals.

Electrocardiography↗

Maturation of ventilation and ventilatory pattern in normal sleeping infants.

Noninvasive studies of ventilation and ventilatory pattern were performed serially in 15 normal infants in the first 4 mo of life during REM and quiet sleep with the barometric method. We measured tidal volume (VT), total respiratory cycle time (Ttot), inspiratory time (Ti), expiratory time (TE), mean inspiratory flow (VT/TI), and respiratory "duty cycle" (TI/Ttot). Vt, Ttot, TI, TE, VT/TI, and VT/Ttot but not TI/Ttot increased with age. In all age groups, Ttot, TI, and TE but not VT/TI were greater in quiet than in REM sleep. In the first 2 mo of life, VT was greater in quiet than in REM sleep; in the older infants, VT/Ttot was smaller in quiet than in REM sleep. TI/Ttot was not dependent on sleep state. Thus, because VT/Ttot = VT/TI X TI/Ttot, the increase in VT/Ttot with age results from an increase in mean inspiratory flow rather than from changes in respiratory "duty cycle". Further, the "on-switching" as well as the "off-switching" of inspiratory activity depends on sleep state.

Aging↗

The QT interval in aborted sudden infant death syndrome infants.

The QT interval was measured in 12 normal and 7 aborted sudden infant death syndrome (SIDS) infants in rapid eye movement (REM) and quiet sleep at monthly intervals through the age of 4 months. An accuracy of better than 2 msec was assured by high resolution of the digitized signal and calibration of each QT measurement with an accurately generated time code. In contrast to current speculations, the QT index was significantly smaller in the infants with aborted SIDS than in the normal infants in both REM and quiet sleep (P less than 0.05). In addition, as in normal infants, the QTc was smaller in REM than in quiet sleep (P less than 0.01). Although these results offer no support for the hypothesis that SIDS results from prolongation of the QT interval, they suggest that aborted SIDS infants have a functional abnormality in the autonomic nervous system.

Autonomic Nervous System↗