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Biomedical subjects

M A Epstein

Publications and source records attributed to M A Epstein.

At least 127 records · Page 7Linked to original sources

Effect of sleep state on the QT interval in normal infants.

Twenty QT intervals selected at random from the middle periods of rapid eye movement (REM) and quiet sleep were measured in 12 normal infants studied at 2 weeks and 1, 2, 3, and 4 months of life. A digitizing system, consisting of a precision rotational potentiometer mounted on a pair of calipers and an A/D converter, was used for measurements. An accuracy of +/- 2 msec was achieved by high resolution of the digitized signal and calibration of each QT measurement with an accurately generated time code. Sleep staging was done visually using an electroencephalogram (EEG), an electrooculogram (EOG), a submental electromyogram (EMG), and behavioral criteria. Our results show that the QT index (QTc = QT/square rootRR) was significantly greater during quiet sleep (mean = 0.439) than during REM sleep (mean = 0.433) (P less than 0.01) and that this difference existed at all ages studied.

Electrocardiography↗

A theoretical analysis of the barometric method for measurement of tidal volume.

The barometric method is unique in allowing measurement of tidal volume in a manner that requires no tactile contact with the subject. The equations used by previous investigators to calculate tidal volume described only events occurring during inspiration. Neglect of events during expiration caused a systematic error. Additional equations needed to calculate tidal volume for the barometric method are derived. An error sensitivity analysis is performed to assess quantitatively the accuracy of the calculated tidal volume due to propagation of errors in the experimentally measured variables. Numberical evaluation for typical cases indicates that the limit of accuracy for tidal volume measurement lies between 10 and 15%.

Humans↗

Cytogenetics of malignant epithelial cells and lymphoblastoid cell lines from nasopharyngeal carcinoma.

The malignant epithelial cells of nasopharyngeal carcinoma (NPC) and cells of lines derived form the lymphoid cells which infiltrate this tumour have been investigated cytogenetically. Chromosome spreads of lymphoblastoid cells of lines established from 7 different NPC biopsy specimens were examined after banding staining. Banding was also applied to the epithelial tumour cells of 5 further biopsy specimens freed from non-malignant infiltrating cells by passage through nude mice; epithelial cell spreads were obtained by in vivo splindle arrest. Five of the lymphoblastoid lines were found to be diploid, and 2 tetraploid; the karyotypes were essentially normal. The squamous epithelial nature of the cells in the nude-mouse-grown NPC tumours was established by light and electronmicroscopy, and 3 tumours were found to be near-triploid, and 2 near-diploid. The cells of the near-triploid tumours contained grossly abnormal chromosomes but those of the near-diploid tumours showed only relatively minor changes. Although abnormalities were observed which were specific for cells from each individual tumour, no discernible change was common to cells from all the tumours.

Adult↗

Congenital failure of automatic control of ventilation, gastrointestinal motility and heart rate.

A new congenital syndrome characterized by the simultaneous failure of control of ventilation (Ondine's curse) and intestinal motility (Hirschsprung's disease) is reported in three infants, all of whom died in the first few months of life; two were siblings. Detailed studies in one also revealed markedly decreased esophageal motility and abnormal control of heart rate. In one infant, minute ventilation was lower in quiet than in REM sleep and lower in both states of sleep than in wakefulness. Although the mean inspiratory flow was decreased in quiet sleep, the hypoventilation resulted primarily from a decrease in respiratory frequency. Intravenous doxapram increased ventilation but did not reverse respiratory failure. Aminophyllin, progesterone, physostigmine and chlorpromazine did not change ventilation significantly; imipramine resulted in a significant decrease. Both long and short-term variability of the heart rate were markedly decreased when compared with the normal infant. Although neuropathologic studies postmorten did not reveal an anatomic defect, we postulate that a developmental abnormality in serotonergic neurons is responsible for this new syndrome.

Doxapram↗

Epstein-Barr (EB) virus genome-containing, EB nuclear antigen-negative B-lymphocyte populations in blood in acute infectious mononucleosis.

Experiments have been performed to identify the type and size of cell infected by EB virus in the blood of acute infectious mononucleosis (IM) patients, and to investigate the nature of the infection. Virus-infected cells, recognized by their ability to give rise to lymphoblastoid cell lines when co-cultivated with foetal lymphocytes, were shown to be restricted to the B-lymphocyte population. Samples of this population from each of eight IM patients were found to be negative for EB nuclear antigen (EBNA) staining. Thereafter, fractions of IM B-lymphocytes prepared on the basis of cell size were assayed either by co-cultivation, for the incidence of virus-infected cells, or by immunofluorescence staining for the presence of cells expressing EBNA. The great majority of virus-infected cells were found in the fractions of normal sized B-lymphocytes and yet these fractions were unequivocally EBNA-negative B-cell populations in IM blood is discussed in terms of the type of infection established by EB virus in the circulation of IM patients.

Adolescent↗

Preliminary seroepidemiological studies on the human syncytial virus.

The seroepidemiology of the human syncytial virus was investigated by means of an indirect immunofluorescence test on 241 sera from Kenya, Tunisia, Singapore and Britain. These included sera from patients with nasopharyngeal carcinoma, other tumours of the oro-nasopharynx, tumours of other parts of the body, and from normal donors. In this study, the virus was found to infect only Kenyan Africans and all but one of these seropositive subjects had tumours, particularly of the oro-nasopharyngeal spaces. The significance of these findings is discussed.

Adult↗

Sensitivity of the transforming and replicative functions of Epstein--Barr virus to inhibition by phosphonoacetate.

Disodium, phosphonoacetate (PA), at concentrations of 50 to 200 microgram/ml, which still allowed continued growth of the EB virus-transformed B95-8 cell line on a routine culture regimen, was able to inhibit the production of virus capsid antigen and of virus particles by these cells down to very low but finite levels which persisted despite prolonged treatment. Further experiments measured the effects of these same drug concentrations on the EB virus-induced in vitro transformation of foetal cord blood lymphocytes and on the colony forming ability of already established EB virus-transformed foetal cell lines; in both types of culture, doses of PA up to and including 50 microgram/ml did not affect cell growth within the 8-week observation period, whereas doses of 100 microgram/ml and above were increasingly inhibitory. The cell lines established by EB virus-induced transformation in the continual presence of PA at 50 to 150 microgram/ml contained multiple copies of the virus genome per cell just as did the corresponding cell lines established in control medium. The results argue against the existence of any PA-sensitive event unique to the EB virus-induced transformation process.

Antigens, Viral↗

Cytogenetic observations on the malignant epithelial cells and infiltrating lymphocytes of nasopharyngeal carcinoma.

Because of the presence of a No 14 chromosome marker abnormality in EB virus-carrying cells from African Burkitt's lymphoma (BL) but not from other origins, and the association of EB virus with nasopharyngeal carcinoma (NPC) as well as BL, both the malignant epithelial cells and the non-malignant lymphoid cells of NPC have been investigated cytogenetically. Chromosome spreads from seven NPC-derived lymphoblastoid lines were examined after banding; five lines were diploid and two were tetraploid. No consistent no. 14 chromosome abnormalities were found. Apart from a secondary constriction near the centromere of both no. 1 chromosomes in all cells of one diploid line, no consistent significant abnormalities were seen. Five NPC tumours, freed of infiltrating lymphoid cells by passage through nude mice, were similarly examined after spindle arrest in vivo. Two tumours were near-diploid, and three were hypo-tetraploid. Near-diploid cells had only minor chromosomal changes, but the hypotetraploid spreads from all tumours showed gross changes of uncertain origin, including frequent, major translocations. No. 14 chromosome marker changes were not seen, and there was no other consistent pattern of abnormality in tumour cells.

Animals↗

Mechanism of the establishment of Epstein-Barr virus genome-containing lymphoid cell lines from infectious mononucleosis patients: studies with phosphonoacetate.

A concentration of disodium phosphonoacetate (PA) has been defined which will reduce the synthesis of infectious EB virus in a producer cell line to 1% of control values but which will not affect the growth of EB virus-transformed cells in a 12-week colony-forming assay. When total mononuclear cells or T-lymphocyte-depleted mononuclear cells from the blood of acute IM patients were cultured in the presence of PA at the above concentration, the regular establishment of EB virus genome-containing cell lines seen in control cultures was almost totally abolished. In further experiments, when T-lymphocyte-depleted IM mononuclear cells were co-cultivated with foetal cells of the opposite sex in the presence and absence of PA, cell lines of mixed or of exclusively foetal origin were obtained not only from control co-cultures but also on those rare occasions when transformed foci developed in PA-treated co-cultures. The results suggest that all cell lines derived from the blood of IM patients are initiated in culture by a two-step process of virus release and secondary infection, and argue against the occurrence of any direct outgrowth of IM cells transformed by the virus in vivo.

Antigens, Viral↗

Isolation of infectious EB virus from the epithelial tumour cells of nasopharyngeal carcinoma.

Evidence of herpesvirus replication has been found by light and electron microscopy in the malignant epithelial cells of two out of six nasopharyngeal carcinomas (NPC) examined directly after growth in nude mice to eliminate non-malignant infiltrating cells. The agent has been identified as EB virus by immunofluorescence tests for EB virus capsid antigen, and has been shown to be biologically active by its ability to infect and transform foetal cord blood lymphocytes. Lymphoblastoid cell lines which express the EB virus nuclear antigen have been established from the transformed foetal lymphocytes, and thus carry the first isolate of the virus from the actual epithelial tumour cells of NPC, in a form suitable for further investigation. The results are discussed in terms of the relationship of EB virus to NPC epithelial cells.

Adult↗

Comparative studies on adult donor lymphocytes infected by EB virus in vivo or in vitro: origin of transformed cells arising in co-cultures with foetal lymphocytes.

Co-cultures were set up between equal numbers of mononuclear cells from the blood of EB virus-infected individuals, either acute IM patients or healthy seropositive adult donors, and foetal cord blood mononuclear cells of the opposite sex. The cell lines arising in the co-cultures were of mixed origin, with foetal cells predominating in many cases. In contrast, when mononuclear cells from seronegative adult donors were first infected with EB virus in vitro and then 5 to 12 days later co-cultured with a large excess of foetal cells of the opposite sex, the cell lines which arose were almost exclusively derived from the adult donor despite the fact that a small minority of the virus-infected adult cells released infectious virus capable of transforming the co-cultivated foetal cells. The experiments suggest that EB virus-infected cells present in the blood of IM patients and seropositive donors do not possess the capacity for unlimited in vitro growth shown by seronegative adult donor lymphocytes experimentally infected with the virus.

Adult↗

Sequential immunofluorescence and infectivity studies on the replication of Herpesvirus saimiri in owl monkey kidney cells.

Methods are described for the preparation and authentication of a highly specific antiserum against herpesvirus saimiri (HVS) capsid antigens. The antiserum was used in immunofluorescence tests to follow the development of capsid antigens in HVS-infected owl monkey kidney cells throughout the virus replication cycle in parallel with sequential titrations of virus infectivity in both cells and medium. Fluorescence was detected as a round or oval, bright green area of staining at the centre of the nucleus which was similar in outline to the Cowdry type A inclusion seen in HVS-infected cells stained by haematoxylin and eosin. The first detection of fluorescence towards the end of the eclipse phase of the virus growth cycle, and its abolition by the treatment of infected cultures with cytosine arabinoside confirmed the identity of HVS capsid antigens as late antigens. The failure to detect fluorescence in the cytoplasm of HVS-infected cells has brought to light a conflict between the site of accumulation of virus capsid antigens as determined by immunofluorescence and the finding, by electron microscopy, of cytoplasmic immature particles in intact cells during the early stages of the virus replication cycle. The significance of this discrepancy is discussed in relation to its possible existence for other members of the herpesvirus group.

Animals↗