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Anti-herpesvirus effects of Isoprinosine were found to be condition-dependent in vitro and in vivo. A herpes type 1 strain, grown in primary rabbit kidney cells, was not susceptible to Isoprinosine when cytopathic effect was evaluated, but was modestly inhibited when plaque-forming methocel overlay was used in the same cell line. However, the growth of a herpes type 2 strain was inhibited by Isoprinosine in this system when cytopathic effect was evaluated. Both viruses produced an encephalitis in hamsters after application by corneal abrasion. The encephalitis produced by a 1.5 mean lethal dose of herpesvirus was strikingly suppressed by large doses of Isoprinosine given ad libitum in the drinking water; this protection was not seen, however, at 15 mean lethal doses. Anti-herpes effects of Isoprinosine were suppressed by additional treatment with cortisone, both in tissue culture and in vivo. Isoprinosine, in the absence of virus infection, produced significant effects on the metabolism, structure, and function of brain ribosomes. In vivo, RNA components were labeled more rapidly and gave up their radioactivity more slowly after treatment with Isoprinosine. This enhanced cytoplasmic radioactivity was associated with a loss of incorporated radioactivity located in the nucleus and an increase in radioactivity located in a ribonucleo-protein fraction >4 S and S . Ribosomes from treated brains gave physical evidence of being more compact (less orthochromic). Isoprinosine treatment increased the incorporation of [ 14 C]phenylalanine into nascent protein in a cell-free system examining protein synthesis in brain polyribosomes. The addition of the exogenous messenger ribonucleic acid, polyuridylic acid, produced a significant age-dependent inhibition in the incorporation of [ 14 C] phenylalanine. This inhibition was significantly greater when ribosomes were isolated from animals pretreated with Isoprinosine. These and other observations suggest that the Isoprinosine stimulation of host ribonucleic acid metabolism may be coupled to the production of ribosomes that do not effectively translate exogenous messenger ribonucleic acid.

The injection of extracts of leukemic and Hodgkin’s disease tissues of man elicit an antibody reaction in both man and rabbit. This response is similar to that elicited by leukemic mouse tissues when injected into rabbits. The antibody reaction may be demonstrated by the technics of passive cutaneous anaphylaxis, immunodiffusion, microprecipitin and immunofluorescence. Tissue extracts from non-leukemic individuals do not elicit a similar response. Rabbits immune-tolerant to normal human tissues produce antibodies specific to leukemic human antigens. Antibodies develop in those individuals who are exposed for a long time to either human or mouse leukemia. These immunologic studies demonstrate specific antigenic differences between normal and leukemic tissue extracts. It is postulated that the difference between normal and leukemic extracts is the consequence of the presence of viruses or the alterations caused by them.

A hypothesis predicting that increase in the rate of synthesis of host messenger RNA would be associated with antiviral activity was examined. Biochemically, Isoprinosine or NPT-10381 (methisoprinol) increased the rate of rapid labeling of polyribosomal RNA and protein in uninfected monkey kidney cells in tissue culture. In tissue-culture systems, Isoprinosine exerted antiviral effects against influenza virus, PR-8 and A2 strains; herpes virus, LU strain; polio virus 3; and adenovirus 10. In in vivo mortality studies, Isoprinosine was observed to exert therapeutic antiviral effects against the A2 strain of influenza and, as well, against a herpes infection of newborn mice. Experiments were carried out which demonstrated a correlation between the in vivo anti-influenza (PR-8) effects of Isoprinosine and reduction in the virus titer in lungs of infected mice.

This experiment investigated the predictability of pause time in a 1537 word spoken message. A professionally read rendition paced at 164 wpm was analyzed from three points of view: ( a ) an immediate constituent, or surface structure, syntactic analysis; ( b ) a stochastic information analysis of all lexical items in context; and ( c ) a deep structure analogue or clause analysis. Results indicated that 64% of the pause variance could be predicted from the syntactic measures. Both the surface structure and deep structure analogue measures of syntactic complexity yielded reliable predictive variance not accounted for in the overlap of the two variables, suggesting that both levels of linguistic representation were important determiners of pause structure in an oral reading performance.

Various physicochemical characteristics and the biological activity of two murine lymphoma viruses (S-63 and GC), originally isolated in this laboratory and previously reported as sharing common antigenic properties with human and bovine lymphomas, are defined. These viruses are stable at temperature ranges from −70 °C to +4 °C and are inactivated after incubation at +56 °C for 30 min. They withstand lyophilization and are inactivated by treatment with ethanol, acetone, ethyl ether, formalin, and phenol. Both agents are of the ribonucleic acid, double-membraned viruses, similar to myxoviruses, and are approximately 100 mμ in size.

SummaryA fluorescent-antibody system is reported which allows rapid analysis of the minor antigenic differences between mouse mammary tumor agent (MTA) extracts obtained from different sources. This method correlates very well with the bio-assay method reported by Bittner and associates. An analysis of the antigenic component can be made within a few hours after receiving the MTA extract. In the older bio-assay method up to 2 years of observations were necessary for proper evaluation. The disadvantages of the fluorescent-antibody system include, a) interference by non-specific fluorescence, b) limitations imposed by antisera employed, c) removal of normal tissue antibodies, and d) selection of appropriate fluorescent dyes for conjugation to the sera. These disadvantages can be partially overcome by carefully selecting the antigens to be used for preparing antisera, adsorption of antisera with mouse liver powder extracts, concentration of globulin fractions prior to conjugation, and use of sharply contrast...

Alterations for acid and alkaline phosphatase levels and their pattern of splenic and lymph node activity in normal and virus-induced lymphoblastic leukemia were studied. Enzyme levels were examined by using both cytochemical and biochemical procedures. The GC leukemia virus, a ribonucleic acid murine virus antigenically related to the Rauscher-Moloney viruses, was used to stimulate acid and alkaline phosphatase by producing lymphomaceous disease in Ha/ICR mice. With the Burstone and Gomori cytochemical procedures, both enzymes were found in higher than normal levels in lymphomaceous spleen and lymph nodes. Confirmation of the cytochemical studies was obtained by enzyme assay of cell-free homogenates in each case with the exception of spleen acid phosphatase. The discrepancy between the cytochemical tests which showed significant elevation of spleen acid phosphatase and the enzyme assays which failed to reveal such elevation could be due to a labile acid phosphatase isozyme which is lost on cellular disruption during homogenate preparation. A significant spleen alkaline phosphatase specific activity elevation above normal was found with a 50% incidence only when leukemic spleen wet weight increased nearly threefold its normal value. This result suggests that alkaline phosphatase elevation is a secondary event occuring after the onset of disease and is not a fundamental metabolic alteration concerned with the onset of murine lymphoblastic leukemia.

The present studies are an extension of earlier reports on the antibody response of mice to a leukemogenic virus (S-63). These investigations were designed to show whether a correlation exists between in vivo and in vitro determinations, and whether protective antibodies against the virus could be produced in immune-tolerant animals. Viral neutralization and protection studies in mice were compared with passive cutaneous anaphylaxis (PCA), immunodiffusion, microprecipitin, and immunofluorescent tests using similar antigens and antibodies. As shown in tables 1, 2 and 3, antibody could be demonstrated by both in vivo and in vitro methods, and these studies showed (table 2) that the antibody was protective. The S-63 leukemia virus was isolated in 1963 from a mouse ascites cell leukemia line. That cell line had been carried in the laboratory for over 3 years. The virus has been carried in ICR mice since its isolation. Immunologic studies were carried out to determine the relation between the virus and the originating ascites cell. Studies of antibodies produced in normal rabbits against the S-63 virus were unsatisfactory for purposes of these experiments because of cross reaction with normal mouse tissue. Immune-tolerant animals have yielded valuable information: Antibodies produced in immune-tolerant rabbits injected with the S-63 virus do not cross react against intact ascites cells from which the virus was originally isolated. Conversely, antibodies similarly produced against the ascites cells do not react against the virus antigen. Antibodies produced in immune-tolerant rabbits against ascites cells protect mice against ascites cell-induced leukemia, but not against the disease induced by S-63 virus. Mice challenged with ascites cells and treated with antiascites cell gamma globulin are protected against the disease. The best therapeutic advantage is obtained when treatment is started either at the time of cell inoculation or in the early stages of the disease. Antibodies which protect newborn animals from infection develop in adult ICR mice recovering from S-63 virus leukemia. These antibodies produced by convalescent mice are similar, from the standpoint of protection, to those produced in immune-tolerant rabbits.

Antikorper bei genesenden Mausen nach Infektion mit Leukamie-Viren (S-63) erzeugt, zeigen eine Kreuzreaktion mit den Leukamie-Antigenen aus Rinder- und Menschenserum und Gewebe. Diese Befunde sprechen dafur, dass die Viren-Antigene in den drei Systemen sehr ahnlich sind.

We undertook an extensive review of world-wide clinical reports of leukemia in twins. Our survey was a careful one; exclusions are inevitable, but, if so, are inadvertent, except for undocumented “personal communication” cases. These have sometimes been included in large reviews of either leukemia or leukemia in twins. Also excluded are cases mentioned only tangentially in reports of cancer in large population groups, if no clinical details were given. In some instances, we were able to adapt available clinical information to our tables.Leukemia appears to occur at four periods in the lives of twins: (1) the perinatal-congenital period; (2) early childhood; (3) late childhood; and (4) adulthood. Those cases occurring around the time of birth and the first year of life are combined under the title: Perinatal-Congenital. In Tab. I, Early Childhood extends from about 2 to 7 years, and Late Childhood from 7 through 12 years. All other cases have been considered as Adult. Two cases occurring in teenagers have been placed in this group in accordance with clinical practice. We have compiled 62 cases of leukemia in twins from clinical reports from the world publications in the following categories: Perinatal-Congenital, 15; Early Childhood, 26; Late Childhood, 9; Adulthood, 12. Comparative clinical details of all these cases will be published in a subsequent report.Except for those instances about which writers admitted that the diagnosis of zygosity was in question, most reported clinical cases occurred in MZ twins. There were 39 cases of leukemia in MZ twins, 13 cases in DZ twins and 10 cases in whom zygosity was in doubt.

Recently there has been increasing interest in the immunological treatment of cancer. The ultimate aim of the immunologist is to produce an active immunity against cancer. However, the more limited goal of treatment using the principle of passive immunity is now being extensively investigated. Recent work by other workers has shown that it is possible to produce anticancer antibodies in another species of animal, and these antibodies are active when injected back into the animal from which the tumor was derived. The antibodies have been labeled with radioactive iodine and with fluorescein and have been shown to react with the tumor tissue both in vivo and in vitro. These anticancer antibodies appear to be present mainly in the γ-globulin fraction of the plasma. In 1954, Nungester and Fisher 1 prepared an anticancer serum which was effective in decreasing the number of tumor "takes." They gave six injections of a filtrate

Brown, Eric R. (Northwestern University Medical School, Chicago, Ill.), Peter Buinauskas, and Steven O. Schwartz . Immunofluorescent antibody studies of a murine leukemia virus. J. Bacteriol. 92: 978–982. 1966.—Correlation was close between in vitro complement fixation, immunodiffusion, and passive cutaneous anaphylaxis tests with the S-63 and GC murine leukemia viruses and immunofluorescence reactions with these viruses. When fluorescein-isothiocyanate-conjugated convalescent sera obtained from mice initially infected with S-63 leukemia virus were used, the reactive site was within the cytoplasm of the infected cell. By electron microscopic examination, virus particles were demonstrated in the same areas within the cells that exhibited specific fluorescence with the conjugates. Spleen and mesenteric nodes contained the most virus, whereas kidney tissues contained the least amount. Fluorescence was not observed within the nuclei of infected cells.

SummaryThe serum protein patterns of 55 patients with various neoplasms were compared by specially stained disc electrophoresis with patterns obtained from 29 control sera. Two control bands, repre...

SUMMARYA review of 62 cases of leukemia in twins reveals most cases occurred in MZ twins, although diagnosis of zygosity was at times admittedly questionable. Concordance was clearly highest in MZ twins of the perinatal-congenital period. This tendency was not maintained at later stages of life.The older concept of a human placental barrier has been greatly modified. Tracer substances have demonstrated that leukemic cells pass the placental barrier. Materno-fetal transmission of leukemia is well known; all forms of murine leukemia can be transmitted similarly from generation to generation. Certain requisites effect the transmission of neoplastic-hematopoietic disease during pregnancy. Rare cases are reported of pregnant women with leukemia who bear children in whom clinical leukemia subsequently develops. The maternal diagnosis was made at the time of, or shortly after, delivery, suggesting an evolution of the maternal disease late in pregnancy.That both partners of a pair of twins, either MZ or DZ, can become ill with leukemia within days or months of each other, appears more than coincidental. Chromosomal defects, common environmental factors, and conjoined intrauterine circulations may be important in the transmission of leukemia from one twin to another, a theory supported by the frequent concordance during the first year of life.

Eight cases of childhood leukemia were diagnosed in a small community. Blood was obtained from members of these and four other leukemic patients' families. The sera were tested for antibodies to leukemic antigens. Antibodies were present in one to three members of every family. Positive reactors most often were the mother or a sibling closest in age to the patient with leukemia. Antibodies were not found in control sera or in patients with leukemia. We interpret these findings to mean that exposure to leukemogenic viruses leads to the formation of antibodies in some and leukemia in others. Not all those who fail to develop demonstrable antibodies develop leukemia, which suggests that present techniques of demonstrating the antibodies may be inadequate. The absence of antibodies in patients with leukemia is, on the other hand, thought to be part of the disease syndrome.

Although published reports of cancer in twins are not numerous, there are case reports of concordance in a variety of tumors in twins. Cancer of the breast is most frequent; concordance has also been noted in uterus, gonads, eyes, stomach and rectum. In general, these reports tend to support the theory that genetic factors operate either in the concordance of cancer or in the site of the specific tumors. The significance of concordance remains in doubt, however. Reported study groups are not comparable because the materials and methods are disparate. In many reviews the methods of zygosity determination are questionable. The fact that not all cases of cancer in twins are reported introduces a constant source of bias. The following review illustrates this well.In 1940, Madge T. Macklin reviewed the publications of tumors in MZ and DZ twins and concluded that tumors affected MZ twins far more than both members of a DZ pair. She observed concordance in tumor type, site, and age of onset, as more frequent in MZ than DZ twins. She later (1947) reexamined the same material and some additional twin pairs and concluded that MZ twins have identical tumors far more frequently than DZ twins. She emphasized that rare types of tumors were genetically determined.In 1948, Busk et al reported on a series of 185 twin study pairs from the Danish Cancer Registry; they concluded that (1) there was a tendency toward a higher incidence of cancer in partners of MZ than of DZ cancerous twins; (2) these deviations from expected values were not considered statistically significant; and (3) there was a tendency for tumors in MZ twins to affect corresponding organs in both partners, this being not the case in DZ twins.

Publisher Summary This chapter focuses on the organization of serial pattern learning. It discusses several theoretical formulations and reports a series of experiments on serial integration of spatially arranged events. According to the association theory, if serial learning is handled by successive associations of one element with the next, then the subject must encounter difficulties in learning any sequence in which the same element is followed by two different elements. A subject cannot use associations to solve a branching sequence unless he has already integrated a series of previous events together into a cue or stimulus. A second theory of serial learning is that the whole sequence can be held in memory as an image, with some sort of “pointer” indicating the current location of the performer. This approach resolves many of the difficulties found in the association theory. Repetition of an element within a sequence may not produce great difficulties, provided that the element is swallowed up by organizational or “Gestalt” qualities of the sequence as perceived. Recent mathematical theories of learning have emphasized short-term memory, including the possible role of rehearsal in fixating serial learning.

Summary In our experiments, histamine did not play a major role in increasing the number of tumor takes in rats inoculated with an approximately 50% take level of Walker 256 cells. Conversely, antihistamines were found to cause a marked enhancement of takes, confirming the fact that tumor substances contain antihistaminics which are important in the enhancement of Walker 256 tumor in rats. Vitamin B 12 may have a role in enhancement of takes in this experimental system. Reserpine, the serotonin antagonist, had significant effect in decreasing tumor takes.

The multiplication and release into the medium of a murine leukemic virus (GC) occurs in mouse embryo tissue cultures. Autoradiographic analysis of such infected and uninfected cultures after 24-h labeling periods with uridine-5-H3 demonstrated extensive nuclear and cytoplasmic activity. Such activity was always more extensive in infected cultures, indicating that they were more metabolically active than uninfected cultures. The cytoplasmic activity was apparently in single-stranded RNA, since it was completely removed with pancreatic RNase. A portion of the nuclear label which was RNase-resistant was in DNA, since RNase followed by DNase, or the reverse, removed all label.Autoradiographic analysis of cultures given pulse labels of uridine-5-H3 from 5 to 60 min revealed only nuclear label, always more extensive in infected cultures. This indicates that the synthesis of "rapidly labeled" RNA is enhanced by viral infection; this occurs even within 2 h after infection. Nuclear activity observed after 5- and 10-min pulses was removed by buffers containing RNase or DNase. Possibly this label was in diffusible low molecular weight species of RNA. After 30-min pulses, activity was exclusively associated with pancreatic RNase-sensitive single-stranded RNA. After 60-min labeling, tritium from uridine-5-H3 was taken up into nuclear DNA in addition to RNA.

For the initial six trials of a two-category concept-identification task, Ss were told “right” regardless of their response (R), told “right” and “wrong” randomly (RR), or given no feedback (NF), and the value of the to-be-relevant dimension either remained constant (C) or varied randomly (V). Performance after R and RR was significantly inferior to performance after NF, but R and RR did not differentially retard learning. Neither the C-V factor nor its interaction with type of feedback reached significance. These results were said to be compatible with the idea that Ss use memory to eliminate hypotheses in concept identification.

In learning a repeating serial pattern of six lights, college students divided the event sequence into recurring subunits such as runs (1 2 3 4) and trills (3 4 3 4). The experiment showed that an ambiguous serial pattern (2 1 2 3 4 3 4 5 6 5) would be organized into runs, 2(1 2 3 4) (3 4 5 6)5, by Ss pretrained on a pattern of runs, and into trills, (2 1 2) (3 4 3 4) (5 6 5), by Ss pretrained on a pattern of trills. The profile of errors and the frequencies of run- and trill-overextension errors were symptomatic of how the test pattern was organized.

La methode d'electrophorese en gel avec coloration speciale est utilisee ici pour la comparaison des proteines seriques de 97 malades porteurs de neoplasme avec celles de 33 contrOles normaux. Deux bandes, presentes dans tous les contrOles representant aux moins deux differentes proteines avec une mobilite d'α-2-globuline, sont absentes dans 60 serums de malades.

Attempts were successful to develop tissue culture cell lines of murine origin capable of supporting the GC and S63 murine viruses. Viruses from this source were used as antigens to prepare antisera in rabbits. These sera cross-reacted with Moloney, Friend, and Rauscher antigens prepared similarly; however, dilution techniques disclosed that the S63 and GC viruses contain a specific antigen not related to the Rauscher, Friend, Moloney agent. Attempts to grow these two agents (S63 and GC) on J111 cells (a human leukemia) failed.

To the Editor:— The recent article on pagophagia and the accompanying editorial comment ( 207 :513, 1969; 207 :552, 1969) point out one of the most preplexing aspects in the study of the many forms of pica. This problem is to determine whether the associated anemia is the cause of perversion of the appetite or whether perversion of the appetite indeed causes anemia. While it is tempting to look for a direct cause and effect relationship, critical examination of the many available reports does not settle the question. We agree wholeheartedly that it would appear prudent to keep an open mind to the possibility that many factors may be operational at the same time. We have begun to reexamine our own material and premises in this area. Our original article noted an absolute incidence of 34.6% of 1,000 obstetric patients admitting to amylophagia during pregnancy ( Obstet Gynec 32 :415, 1968). An