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Ameloblastic fibrosarcoma, the malignant counterpart of the ameloblastic fibroma, is a rare odontogenic tumor characterized by benign epithelium and a malignant fibrous stroma. We have compared nuclear DNA content of five ameloblastic fibrosarcomas and three ameloblastic fibromas by image analysis. The three ameloblastic fibromas were diploid, whereas 1 of 5 ameloblastic fibrosarcomas was aneuploid. There was no correlation with histologic grade and aneuploidy. These five new cases were also added to a review of the literature, bringing the total cases of reported ameloblastic fibrosarcomas to 51. The ameloblastic fibrosarcoma occurs at a later age (mean, 27.5 years) compared with reported ameloblastic fibromas (mean, 14.6 to 22 years), which supports a step-wise malignant transformation. There was histologic documentation that 44% of ameloblastic fibrosarcomas developed in ameloblastic fibromas. In view of this data and of the reported cumulative recurrence rate of 18.3% for ameloblastic fibroma, it is recommended that ameloblastic fibromas be treated with complete surgical excision and long-term follow up rather than simple curettage or enucleation.

A murine model of MHC class II deficiency created by targeted gene disruption was used to investigate whether class II expression influences B cell maturation and function. There appeared to be fewer total B cell precursors, a higher proportion of which were in a very early stage of maturation, in class II-deficient vs control bone marrow; however, the differences did not reach statistical significance. Mature B cells were unaffected; IgM, IgD, B220, and CD5 surface expression were similar in class II-deficient and control animals. Serum Ig determinations revealed that the class II-deficient animals had elevated IgM but decreased IgG1 (and, variably, IgE) compared to control. The antibody response against thymic-independent Ag was intact in class II-animals, as was the in vitro response of small resting B cells from class II deficient animals to stimulation with polyclonal B cell activators. Preactivated T cells were able to induce differentiation and proliferation of class II-deficient, small resting B cells. Together, these data indicate that B cell development, T cell-independent, and T cell-dependent B-cell activation, can occur independently of class II MHC expression.

Leukocytes express a family of high m.w. glycoproteins called leukocyte common Ag (CD45), which are involved in phosphotyrosine signal transduction. Antibodies to different CD45 isoforms distinguish functionally different CD4+ T cell subsets in humans, rats, and mice. Selected protein isoforms are expressed through a process of exon splicing that is cell-type and differentiation-state specific. Splicing of the three variable exons, A, B, and C, which encode amino acids located near the extracellular amino terminus of the protein, potentially results in generation of eight different mRNA transcripts. The purpose of the present study was to determine the relative levels of all eight different CD45 transcripts present in a panel of murine CD4+ T cell lines and normal murine and human CD4+ T cell subsets separated with antibodies to CD45 variable exons. We show, as expected, that the broad features of CD45 surface isoform expression in these cells can be accounted for by the relative amounts of the eight differentially spliced transcripts. Unexpectedly, all the differences in CD45 isoform expression among the CD4+ T cell subpopulations that we measured could be accounted for by differences in the overall level of variable exon expression. We did not see differences among T cell populations in the relative expression of particular variable exons. Exon B was always found in greater abundance than exons C or A. Of the dual exon species, only AB and BC were found in CD4+ T cells. The AC species was undetectable. Human CD4+ T cells, especially those in the naive subset, express higher levels of CD45 variable exons than murine CD4+ T cells.

A group of biblical and patristic scholars and palaeographers met in Lunel, Herault, in June 1995 to discuss the many questions posed by Codex Bezae to our understanding of the use of the Gospels and Acts in early Christianity, and of the text of the New Testament. This collection makes the papers and debates of the colloquium available for a wider discussion. The papers cover two broad areas. The first addresses palaeographical questions. The second covers textual matters, subdivided between the Gospels and Acts. The 24 contributors include J.N. Birdsall, J. Irigoin, L. Holtz, B.D. Ehrman, M.W. Holmes, J.K. Elliott, J.M. Auwers and M.-E. Boismard. There is an introduction by the editors, who also provide analyses of each main section. The range of interests represented by the participants and by the papers has already stimulated fresh developments.

The analysis and results of an occultation of the spectroscopic binary star 1 Vulpeculae by the asteroid (2) Pallas, observed from 130 locations, are presented. Combination of solutions from this and previous occultations shows the triaxial shape of Pallas to be elongated, but not severely, with the ratio of the largest to the smallest axes being less than 1.15. The data provide a separation and a position angle of the secondary component of 1 Vulpeculae and indicate that the star's actual parallax is probably near 0.008 arcsec, half of the published value. The analysis gives a calibration of the accuracy and the reaction time corrections for visual observations of asteroidal occultations. The absence of any confirmed secondary extinctions shows that any satellites of Pallas must be rare or small. The photometric observations seem to rule out a substantial cloud of dust surrounding Pallas postulated previously.

We have been using whole rabbit anti-mouse mu antibodies to study Fc-dependent inhibition of mouse B cell activation by F(ab')2 anti-mu antibodies and antigen-nonspecific helper factors (SN). We show here that this inhibition does not appear to require adherent cells, appears to occur independently of cellular interactions, is reversible, and is not maintained solely by suppressive factors. In addition, occupancy of Fc receptors by rabbit antibody-antigen complexes is not sufficient to inhibit activation by F(ab')2 anti-mu and SN. These observations, in conjunction with the observation that blocking the Fc receptor-binding capacity of rabbit anti-mu antibodies by protein A prevents inhibition, suggest that cross-linking mlg and Fcgamma receptors on B cells prevents activation. However, the F(ab')2 anti-mu and SN-activated B cells become refractory to this inhibition by 48 hr in culture.

The Fc portion of rabbit anti-mouse immunoglobulin (Ig) antibodies interferes with anti-Ig-induced B lymphocyte activation as measured by DNA synthesis on day 3 of culture or maturation to Ig-secreting cells in the presence of soluble helper factors on day 4 or 5. To investigate this Fc-dependent effect at an earlier stage in B cell activation, rabbit IgG anti-mouse mu-chain- or delta-chain-specific antibodies were compared with their F(ab')2 fragments for the ability to induce mouse B cells to undergo blast transformation, as defined by an increase in cell volume during the first 24 hr of culture. Both F(ab')2 anti-Ig reagents induce blast transformation, although F(ab')2 anti-mu antibodies induce a greater size change than F(ab')2 anti-delta antibodies. Whole anti-mu or anti-delta antibodies do not induce blast transformation; however, in the presence of a monoclonal anti-mouse Fc gamma receptor antibody that blocks IgG binding to Fc gamma receptors (Fc gamma R), whole anti-mu or anti-delta antibodies induce blast transformation as well as their F(ab')2 fragments. Because the anti-Fc gamma R antibody alone has no effect on blast transformation, it appears that the simultaneous binding of membrane IgM (or IgD) and Fc gamma R by whole anti-Ig antibodies prevents this early event in membrane Ig-induced B cell activation.

We have shown previously that cross-linking receptors for the Fc of IgG (Fc gamma R) to membrane Ig will inhibit membrane Ig-dependent mouse B cell activation. In this report we have determined which mouse IgG subclasses will mediate this inhibition by using monoclonal mouse anti-p-azophenylarsonate (anti-ars) antibodies to inhibit B cell activation by arsanilated rabbit Fab'2 anti-mouse IgM (arsFab'2 anti-mu). Cell recovery and Ig secretion after 4 days of culture with soluble helper factors and arsFab'2 anti-mu was inhibited by IgG1, IgG2b, and IgG2a anti-ars, but not IgM or Fab'2 anti-ars. In addition, we determined which of the inhibitory IgG subclasses are blocked by the monoclonal anti-mouse Fc gamma R antibody 2.4G2, which we have previously shown prevents inhibition by rabbit IgG anti-mu. These experiments demonstrated that 2.4G2 Fab could block inhibition mediated by IgG2a as well as that mediated by IgG1 and IgG2b. Because it has been reported that 2.4G2 does not bind the IgG2a receptor on macrophages, these data support our previous experiments, which indicated that this inhibition is not macrophage dependent.

Mouse B cells are stimulated to proliferate by Fab'2 fragments of rabbit anti-mouse Ig antibodies. Proliferation is inhibited, however, in the presence of IgG anti-mouse Ig. We have previously shown that this inhibition is mediated by binding of the IgG anti-Ig to receptors for Fc gamma R on B cells. This report describes conditions under which IgG anti-mu or anti-delta will induce proliferation despite Fc gamma R engagement. Culture supernatants of Con A-stimulated, Il-4-secreting Th cell lines, but not of Il-2-secreting Th cell lines, will co-stimulate with IgG anti-Ig to induce small B cells to incorporate [3H]TdR. This co-mitogenic activity is inhibitable by anti-IL-4 antibodies and can also be induced by Il-4 affinity purified from the T cell supernatants or by supernatants containing rIl-4. B cells precultured with Il-4 for 18 h, while still expressing normal levels of Fc gamma R, also proliferate to IgG anti-Ig. We have previously shown that Fc gamma R-mIg cross-linking will inhibit mIg-dependent increases in c-myc mRNA levels. We investigated whether Il-4 allows B cells to respond to IgG anti-Ig by elevating c-myc. The data show that Il-4 has little effect on c-myc mRNA levels in either IgG or Fab'2 anti-Ig-containing cultures.

The 24-hr culture supernatant of Con A-activated spleen cells (SN) contains helper factors that enable maturation to high-rate polyclonal Ig secretion and enhance proliferation in cultures of mouse B cells activated with the F(ab')2 fragment of class-specific rabbit antimouse IgM antibody (anti-Ig). When interleukin 2 (IL 2), also called T cell growth factor, is removed from SN by absorption with an IL 2-dependent cell line at either 4 degrees C or 37 degrees C, all the helper activity for anti-Ig-activated B cells is also removed. Partial removal of IL 2 results in partial removal of helper activity for B cells. However, the IL 2-depleted SN appears to contain another helper factor, TRF, that enables anti-Ig-activated B cell cultures to mature to high-rate Ig secretion. This TRF activity is revealed by adding purified human IL 2 or an IL 2-containing supernatant of a cloned, lectin-activated T cell hybridoma line (FS6-14.13) to Il 2-depleted SN, which restores the polyclonal antibody response to anti-Ig. The hybridoma supernatant by itself supports proliferation of anti-Ig-activated B cell cultures, as measured by an increase in cell number, but not maturation to Ig secretion. This proliferative response is likewise IL 2 dependent, although purified IL 2 with anti-Ig is not sufficient. These experiments define separable combinations of factors acting on anti-Ig-activated B cell cultures, one of which (SN) results in both proliferation and maturation to high-rate Ig secretion, whereas the other (hybridoma supernatant) results in proliferation only. IL 2 appears to be an essential component of both combinations, although the target cell for IL 2 action in this system remains to be determined.

RE the classics doomed? If we ask this question it is because there is a current of unrest in some quarters which it would be futile to ignore. The modern spirit of enquiry is abroad and no mere sentimental consideration is permitted to arrest its activities. Bach, Mozart, Beethoven and many others on whose brows History has set the laurel wreath of wisdom and heroism are subjected to a close scrutiny by those with new ears and new eyes. There is nothing alarming in this. Every reasonable person knows that the verdict of competent criticism is more to be desired than the fulsome flattery of assumption, and the masters will leave the hands of the most rigorous expert with plenty of virtue to their credit. We can understand the man who says in effect, "I have been told Beethoven is a great composer. I am not content with what I have been told. I am going to put the assertion to proof." But we have to face a kind of impatience or dissatisfaction that is manifesting itself at the present time. What are you going to say to the man who tells you that Bach is a bore, Mozart trivial, Schubert sugary, Beethoven tedious? What we must do, I think, is to search for the cause of this sense of dissatisfaction. Is it in the man himself? If it be due to an

WV HAT manner of man is this whose operas are played upon the stages of all the opera-houses; whose choicest melodies, wrenched from their environment with a supreme disregard for the niceties of taste, are pressed into service to provide a harmonious background for the clatter of knives and forks in numberless restaurants and compelled to pay their tribute to modern conditions by being recorded on the gramophone; to whose airs foreign barons sip their after-dinner coffee in international hotels? From the North to the Riviera, from Russia to Buenos Ayres, Puccini is popular. It used to be said that the works of Verdi had at one time or another occupied the boards of every self-respecting opera-house in Europe and America. And it is hardly too much to claim that the same is true of the composer of "La Boheme." "Fortunate man!" we exclaim, thinking of the recognition which has come to him. But it must be remembered that the extent of Puccini's success is not without its drawback. Conventions die hard and there is a lingering romantic notion that the real poet is to be found only in the gutter, the real musician only in the attic. When, therefore, fate plays us a strange trick and we discover the former in easy circumstances and the latter with a good dinner to eat the serious person becomes suspicious. And so it happens that critical attention is turned in another direction. If rumor speak truly, there were days in Puccini's youth when a litre of chianti and an innocent omelette were considerations, but no one can deny that the compensation has been great. Puccini was born in 1858. Though still living, Rossini had written his last work and on the shoulders of Verdi lay the musical reputation of Italy. That the man was worthy of the responsibility to which destiny called him will be acknowledged. The remarkable Pari siamo of "Rigoletto" prophesied the coming of a new era and there were better things to follow. Verdi alone had international fame and, as the years passed, it seemed as though Italy were to be represented only by lesser lights. These there have been in plenty, but two of them deserve something more than passing attention. The younger, Arrigo Boito (b. 1842) a gentle Paduan scholar, is a poet with his right hand and

T HE following remarks are set down here by way of reflection and suggestion and are not offered in any dogmatic spirit. The whole question being subjective, it is capable of being treated only with the greatest latitude, and it will be evident to those who have given the matter a moment's thought that unusual difficulties lie in the path of the historian who would do full justice to the romantic movement. Not the least of the problems meets us as at the very threshold. Probably no two persons have exactly the same conception of what romanticism is. Very often one discovers the critic engaged in a search for a concise, yet adequate definition. Most people have a vague idea that the word romanticism is employed to indicate a work which is not classical, but it is impossible to proceed far with a negation. We are, therefore, forced to ask with Sainte-Beuve, "What is meant by a classic?" One writer, eschewing this method and satisfied with a grand show of authority, tells us that "classicism is routine, romanticism is liberty;" another, with equal confidence, that "classicism is imitation, romanticism is originality." Stendhal argued that all good art was romantic in its day. "Romanticism," he held, "is the art of presenting to people the literary works which in the actual state of their habits and beliefs are capable of giving them the greatest possible pleasure; classicism, on the contrary, of presenting them with that which gave the greatest possible pleasure to their grandfathers." In these assertions, as in Victor Hugo's contention that "romanticism is liberalism in literature," we seem to detect something of the exuberance which characterised the manifestos of the new creed. Such

HE date 1814 is for ever memorable in the annals of fiction. In that year Honore Balzac of Tours went to reside permanently in Paris-Paris, the queen of cities, the manners, customs and intrigues of which he was destined to portray with a never tiring pen. As was to be expected in a world which has little clairvoyant sense of artistic potentialities, no trumpetings and drummings announced his entry. Had, however, some onlooker, graced beyond his fellows with a power of prophecy and a gift of discernment, learnt the future author's name, he would rightly have called the moment historical and marked it upon his tablets. Balzac means much to many. Who would be the creator of a Human Comedy, the historian of manners, must keep his eyes open; he must have at once a large vision and a deep gaze; he must touch life at many points. Balzac did certainly touch life at many points, but only one of them calls for mention here. Few writers have treated music so thoroughly, fewer still referred to it so constantly. Balzac's love of music showed itself at an early age. As a boy he was never tired of extracting weird sounds from a small, red violin and his performances were not at all appreciated by those within earshot. This simple fact is important. The child gave promise of the man and his affection for his instrument seems natural in one who was to write of the art of music with such evident sympathy. Like most young men who set out to make a name by plying a busy pen, Balzac had a thorny path to travel, and it is when reviewing the tale of his successes and failures that we first encounter one who had some direct connection with music. When all others, save his sister Laure, had abandoned him, he found a willing confidante in Madame de Berny. This lady, it will be remembered, was the daughter of a harpist, Henner, who could boast of being a persona grata with Marie Antoinette at the court of Louis XVI. Balzac saw in one of her daughters a thorough musician and it is impossible to believe that music was not often discussed in the de Berny household. This little glimpse is one of many which might be culled from the story of the novelist's life. At one time he is instrumental in obtaining for Count

After 2 base line study nights, hyperglycemia of 43–348% above base line was achieved during early sleep on a third night by constant glucose infusion in 6 normal young men. No significant difference in human growth hormone (HGH) release in sleep occurred between base line (mean peak HGH ±se 17.1±2.9 ng/ml) and infusion nights (13.9±4.2 ng/ml). Thus, release of HGH in sleep is not suppressed by acute hyperglycemia. This suggests sleep release is not a substrate servorhythm comparable to waking HGH release. It may be a primary neural rhythm perhaps facilitating protein synthesis.

Evidence is presented for purity and potency of human growth hormone prepared by ultrafiltration. By analytical ultracentrifugation the material sedimented as a single peak with no evidence of skewing on the leading edge. The preparation was free of serum contaminants except for an extremely low concentration of a material that was detected in the γ-globulin region during immunoelectrophoresis. The contaminant was not γ-globulin. Thyrotropin, follicle stimulating hormone, luteinizing hormone and corticotropin were present in trace quantities. The prolactin activity as measured by the pigeon crop sac assay was approximately 3 IU/ mg. Tibial line and body weight gain assays for growth hormone indicated a potency equal to or greater than 1 USP U/mg. By radioimmunoassay the material was equal in potency to a radioimmunoassay standard. (Endocrinology 84: 332, 1969)

Release of human growth hormone during sleep is significantly related to slow, synchronized stages of sleep and therefore would seem to be controlled by related neural mechanisms. When sleep-waking cycles are reversed by 12 hours, the release of growth hormone with sleep is reversed; thus release does not follow an inherent circadian rhythm independent of sleep.

The effector cell in mouse spleen which mediates natural cytotoxicity against mouse hepatitis virus (MHV)-infected target cells was characterized. The target cells were MHV-infected BALB/c 3T3, and the assay time was 3 hr. The effector cell, designated virus killer (VK) cell for the purpose of discussion, had the following phenotype: lymphocyte morphology, plastic-nonadherent, nylon wool-adherent, nonphagocytic, cyclophosphamide-sensitive; by antibody plus complement (C) depletion studies, it was asialo GM1-, NK 1.2 alloantigen-negative, Thy-1.2-, Lyt-5-, and macrophage antigen-negative; by rosetting techniques, it was Fc receptor-positive and surface Fab+; by flow cytometry (FACS) analysis, it was Lyt-2-, MAC-1-, Ia+, IgG (gamma)+, IgM (mu)+, IgD (delta)+, and B cell lineage antibody B-220+. NK cells, measured for cytotoxicity on YAC-1 cells, were similarly tested and were found to differ from the VK cell in the following properties: nylon wool-nonadherent, asialo GM1+, NK alloantigen-positive, Lyt-5+, surface Fab-, MAC-1+, Ia-, IgG-, IgM-, IgD-, and B-220-. The VK effector cell had a phenotype highly distinguishable from NK cells, effectors most commonly associated with antiviral natural cytotoxicity. The VK cell had a phenotype identical to that of a B lymphocyte and was identified as such. Although the effector cells displayed cell surface antibody, the antibody did not appear to be involved in lysis, because lysis could not be blocked by F(ab)'2 directed against Fab, mu, or delta. Cytotoxicity was more likely associated with recognition of the B lymphocyte surface by the MHV glycoprotein E2, as shown in the accompanying companion paper. This is the first demonstration that natural cytotoxicity can be mediated by B lymphocytes.

We have reported that IL 2 is one of the essential helper factors in culture supernatants from concanavalin A-activated spleen cells or T cell hybridomas that support proliferation and immunoglobulin secretion in B cell cultures responding to anti-immunoglobulin. Here we show that cells in such cultures consume IL 2 and bear high affinity IL 2 receptors detected by binding of purified, radiolabeled IL 2. Induction of high affinity IL 2 receptors depends on addition of both anti-immunoglobulin and helper factors, and does not occur in cultures given only anti-Ig, only helper factors, concanavalin A plus helper factors, or LPS. The majority of IL 2 receptors are on cells that also bear endogenous membrane immunoglobulin, because they are found in the membrane immunoglobulin-positive fraction when cultured cells are separated by fluorescence sorting after overnight culture in the absence of anti-immunoglobulin to allow reexpression of membrane immunoglobulin.

The F(ab')2 fragment of rabbit anti-human F(ab')2 antibodies covalently linked to polyacrylamide beads (anti-Ig beads) acts as a polyclonal mitogen for human B cells in whole peripheral blood mononuclear cells (PBM) or tonsil cells. Activation, measured by the rate of DNA synthesis, is the result of an interaction between the anti-Ig beads and membrane immunoglobulin found on B cells. Excess soluble human F(ab')2 blocks activation with anti-Ig beads. Immunospecifically purified antibodies against IgM or IgD bound to beads activate lymphocytes. Also soluble anti-IgM or anti-IgD can block activation with insolubilized anti-IgM or anti-IgD, respectively, by modulating membrane immunoglobulin. Irrelevant rabbit antihapten antibodies bound to beads failed to activate PBM or tonsil cells. Anti-Ig beads act independently of T cells. The anti-Ig beads lead to activation of B cells without further maturation to polyclonal immunoglobulin secretion.

The physiologic relationships of plasma TSH, T4 and T3 levels measured every 20 min in seven healthy young men and one healthy young woman have been investigated. A nocturnal TSH surge was observed in all subjects on both nights of the 36-48 h baseline observation period. In males the maximum plasma TSH value occurred at 2300 h. The mean peak TSH level was 2.0 +/- 0.3 (se) muU/ml compared with a mean of 1.3 +/- 0.9 muU/ml for the entire baseline records of the 8 subjects. The effect of iv infusion of 32-1000 mug of somatostatin (SRIF) for 1 1/2-3 h was investigated in four of the male subjects during 2 or 4 consecutive nights following the control period. Temporal relationships between the hormonal fluctuations observed throughout the control period and during the nights of SRIF infusion were investigated using time series analysis and Student's t test. Rapid fluctuations of plasma T4 and T3 concentration were noted, even when corrected for changes in total protein concentration, with an average coefficient of variation of 10% for T3 and 12% for T4. No increment of plasma T4 or T3 followed the nocturnal TSH surge nor were the rapid fluctuations of the thyroid hormones altered by the TSH surge. SRIF infusion commencing at 2300 h suppressed the elevated TSH levels (P is less than 0.01) while similar infusions begun at 2100 h blocked the expected nocturnal TSH rise observed during control periods in male subjects. Plasma T4 and T3 levels were not significantly affected by the administration of SRIF. The relationship of the rapid plasma T4 and T3 variations to postural changes was investigated in four euthyroid male subjects. Serum levels of TSH, T4 and T3 and total protein were determined at 15 min intervals while postural changes were carefully monitored. The ratios of T4 and T3 to total protein were relatively stable (3-4% coefficient of variation) when the subjects were kept in a supine and motionless position. A 50 mug bolus infusion of T4 raised the basal T4 level by only 1-2 mug/dl. The data suggest that short-term fluctuation of plasma T4 and T3 result from changes in protein concentration due to hemodynamic responses to alteration of posture and physical activity and not to pulsatile secretion of T4 and T3.