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Temporal variations in the expression of the rasoncogene, and its protein product, were investigated during hexamethylene bisacetamide (HMBA)-induced differentiation of murine erythroleukaemic (MEL) cells. We highlight the fact that when comparisons were made between untreated, proliferating cells and HMBA-treated, differentiating cells using only one time-point, differences, both for the expression of the gene and the protein, were in most cases insignificant; standard deviations were high and the interpretation could be made that HMBA had little effect. Such interpretation fails to take account of the dynamic nature of the system, with single time-point studies giving incomplete information, which can be misleading. Multiple time analyses showed clearly that rhythmic patterns of expression were modulated by the differentiating agent. Time-dependent changes in the expression of mRNA specific to H- rasand N- ras, as well as in the expression of the Ras protein, when measured over periods of minutes or hours, were apparent. HMBA affected frequency and phasing of the rhythms. Regulation of the dynamics in this way may be crucial to the control of cell function and transformation.

Determinations of mRNA and enzyme protein analyses for the protein kinase C (PKC) isoforms, alpha, epsilon and zeta, representing the classical, novel and atypical groups, respectively, in murine erythroleukaemic (MEL) cells revealed the occurrence of cyclic behaviour in expression. Such rhythmicity was not apparent when multiple analyses using only a single time-point were considered; the importance of incorporating a time component into experimental design was demonstrated. On induction of differentiation over a period of five days with hexamethylene bisacetamide, changes in the patterns of expression of mRNA and protein were apparent, as compared with those of untreated, proliferating cells. Modulation of the dynamics of the various PKC isoforms may represent a regulatory mechanism for the control of a diversity of cellular functions.

It has been previously demonstrated that hybrid Ty virus-like particles (VLP) prime effective CD8⁺ and CD4⁺ T cell responses. In this study, we investigated the effect of treating mice with Ty VLP carrying the immunodominant epitope of Der p 1 after sensitizing them to the group 1 allergen of the house dust mite Dermatophagoides pteronyssinus (Der p 1), under conditions that induce T_h2 immunity. We show that i.p. treatment with the hybrid VLP abrogated allergen-specific IL-5 production and reduced allergen-specific cell proliferation. This suppression of the response was mediated by CD4⁺ T cells and was not accompanied by an increase in IFN-γ production.

Enamel-producing cells (ameloblasts) pass through several phenotypic and functional stages during enamel formation. In the transition between secretory and maturation stages, about one quarter of the ameloblasts suddenly undergo apoptosis. We have studied this phenomenon using the continuously erupting rat incisor model. A special feature of this model is that all stages of ameloblast differentiation are presented within a single longitudinal section of the developing tooth. This permits investigation of the temporal sequence of gene and growth factor receptor expression during ameloblast differentiation and apoptosis. We describe the light and electron microscopic morphology of ameloblast apoptosis and the pattern of insulin-like growth factor-1 receptor expression by ameloblasts in the continuously erupting rat incisor model. In the developing rat incisor, ameloblast apoptosis is associated with downregulated expression of the insulin-like growth factor-1 receptor. These data are consistent with the hypothesis that ameloblasts are “hard wired” for apoptosis and that insulin-like growth factor-1 receptor expression is required to block the default apoptotic pathway. Possible mechanisms of insulin-like growth factor-1 inhibition of ameloblast apoptosis are presented. The rat incisor model may be useful in studies of physiological apoptosis as it presents apoptosis in a predictable pattern in adult tissues.

It has been previously demonstrated that hybrid Ty virus-like particles (VLP) prime effective CD8(+) and CD4(+) T cell responses. In this study, we investigated the effect of treating mice with Ty VLP carrying the immunodominant epitope of Der p 1 after sensitizing them to the group 1 allergen of the house dust mite Dermatophagoides pteronyssinus (Der p 1), under conditions that induce T(h)2 immunity. We show that i.p. treatment with the hybrid VLP abrogated allergen-specific IL-5 production and reduced allergen-specific cell proliferation. This suppression of the response was mediated by CD4(+) T cells and was not accompanied by an increase in IFN-gamma production.

The interaction between radioiodinated lipopolysaccharide from Escherichia coli 0111:B4 (125I-LPS) and human peripheral-blood monocytes was studied. The association of 125I-LPS with monocytes at 37 degrees C appeared to depend on binding to the cell membrane with subsequent internalization of the molecule, and was not saturable with time (up to 2 h) or 125I-LPS concentration (up to 10 micrograms/ml). There was no apparent difference in the behaviour of unlabelled LPS and 125I-LPS with respect to monocyte association. 125I-LPS association with monocytes was inhibited by LPS and O-polysaccharide from E. coli 0111:B4 and Salmonella typhi 0901, but not by lipid A or polymyxin B. We propose that the mechanism of human monocyte stimulation by LPS involves polysaccharide-dependent binding to the cell membrane followed by internalization of the LPS molecule. We were unable to demonstrate a specific LPS receptor such as that found on murine B-lymphocytes.

Mitochondrial preparations derived from denervated rat skeletal muscle and paired controls were characterized with respect to their ability to take up externally added Ca2+. The denervated and control muscle homogenates and mitochondrial [Ca2+] were also determined. Our data indicate that the denervated mitochondria are able to take up less Ca2+ than the controls before uncoupling occurs. This defect is associated with elevated [Ca2+] in homogenate and mitochondrial fractions in the denervated state. The causal relationship between Ca2+ overload, mitochondrial functional damage and cell necrosis is discussed.

Burrowing activity was utilized as a measure of the ability of the hard shell clam (Mercenaria mercenaria) and the Atlantic surf clam (Spisula solidissima) to cope with extremes of temperature and dissolved oxygen. Clams were removed from clean sand substrate and the progress of reburial timed. Experiments were conducted in a once through circulating seawater system in which temperatures were maintained at selected (?T) increments above ambient levels.Results of the thermal experiments indicated a zone of optimum activity, above and below which burrowing declined with changing temperature. Thermal optima, upper limits of activity, and burrowing rates were found to be species specific. Long-term effects of dissolved oxygen concentration on burrowing were determined using an apparatus constructed to remove oxygen from seawater and reaerate in controlled increments. Ability of M. mercenaria to burrow, when exposed to oxygen impoverished conditions (less than one milligram of oxygen per liter of seawater) for up to three weeks, was not severely or permanently impaired. Species specific responses to temperature and dissolved oxygen are discussed in relation to habitat and geographic distribution of the clams.

As a possible factor responsible for reduced fever responses in the newborn, we measured plasma cytokine concentrations and cytokine production by neonatal monocytes after lipopolysaccharide or IL (interleukin)-1a stimulation in vitro and compared these data with those obtained from adult plasma and monocytes. Whole blood was collected from afebrile adults (n=12) and the umbilical cord of normal term infants (n=12). Plasma and peripheral blood monocytes were prepared by conventional techniques. Significantly lower concentrations of IL-1a, IL-1ß (P<0.05,t-test) and IL-6 (P< 0.01,t-test) were found in the plasma of newborn babies compared with that of adults. There was no significant difference in plasma tumour necrosis factor (TNF) concentrations between the adults and newborn babies. Monocytes from newborn babies had the capacity to produce IL-1a and IL-1ß as readily as adult cells after stimulation with lipopolysaccharide or IL-1a, and produced significantly lower concentrations of TNF and IL-6 than those produced by stimulated adult monocytes (P< 0.01, ANOVA). Our results suggest that the reduced production of IL-6 by monocytes of the newborn during infection could be partly responsible for attenuated fever responses observed in the neonate.

Immunohistochemistry was used to study the ontogeny of GH receptor/binding protein (GHR/BP) and IGF-I from the 13-day-old embryo (E13) to the E19 rat fetus in the developing incisor and molar. Analysis of serial sections revealed diffuse staining of GHR/BP and IGF-I at the bud and early cap stages within both the mesenchyme of the dental papilla and the ectodermal-erived enamel organ. Just before transition to the cap stage, immunoreactivity of GHR/BP and IGF-I increased in the epithelial bud and extended to the condensed dental mesenchyme. At the cap stage, the dental epithelium showed an intense expression of GHR/BP and IGF-I, whereas the dental mesenchymal cells showed very weak staining. The inner enamel epithelium and the outer enamel epithelium were positive for both GHR/BP and IGF-I in the bell stage. Differentiating ameloblasts, odontoblasts and the secretory ameloblasts and odontoblasts continued to express GHR/BP and IGF-I in incisors. These findings support the premise that growth hormone and IGF-I may play a role in embryonic tooth development by regulating the epithelial-mesenchymal interactions that influence events in growth and cytodifferentiation.

Insulin-like growth factor-I (IGF-I) is a pleiotrophic polypeptide which appears to have roles both as a circulating endocrine hormone and as a locally synthesized paracrine or autocrine tissue factor. IGF-I plays a major role in regulating the growth of cells in vivo and in vitro and initiates metabolic and mitogenic processes in a wide variety of cell types by binding to specific type I receptors in the plasma membrane. In this study, we report the distribution of IGF-I receptors in odontogenic cells at the ultrastructural level using the high resolution protein A-gold technique. In the pre-secretory stage, very little gold label was visible over the ameloblasts and odontoblasts. During the secretory stage the label was mostly seen in association with the cell membranes and endoplasmic reticulum of the ameloblasts. Lysosome-like elements in the post-secretory stage were labelled as well as multivesicular dense bodies. Very little labelling was encountered in the ameloblasts in the transitional stage, where apoptotic bodies were clearly visible. The maturation stage also exhibited labelling of the secretory-like granules in the distal surface. The presence of gold particles over the plasma membrane is an indication that IGF-I receptor is a membrane-bound receptor. Furthermore, the intracellular distribution of the label over the endoplasmic reticulum supports the local synthesis of the IGF-I receptor. The absence of labelling over the transitional ameloblasts suggests that the transitional stage may require the non-expression of IGF-I as a prerequiste or even a trigger for apoptosis.

This study evaluates intracellular cAMP concentrations, in interleukin-l (IL-1) mediated cytostasis of K562 cells. Dibutyryl-cAMP, forskolin, staurosporine and phorbol 12-myristate 13-acetate were all found to mimic the cytostatic action of IL-1 on K562 cells. IL-1 was found to elicit a dose-dependent rise in adenyl cyclase activity in isolated K562 membranes, as well as increasing cAMP concentrations in whole cells. cAMP concentrations were found to peak within 3 minutes of IL-l stimulation. A 27-29% reduction in proliferative activity elicited by IL-1, forskolin and staurosporine, correlated with a 6 fold increase in adenyl cyclase activity, in each case.

The enzyme chinnabarinate synthase was purified from the nuclei of baboon liver. Two purified fractions were obtained that exhibited a typical haem protein absorption spectrum; a probable identity with catalase was demonstrated. It was confirmed that catalase in the presence of Mn2+ produces cinnabarinate from 3-hydroxyanthranilate. Doubt is expressed on the existence of a distinct cinnabarinate synthase enzyme.

Workplace injuries at the University of Queensland Dental School during the period 1992–1994 were assessed to determine their incidence, and the associated indirect costs, causal factors, and appropriate preventive strategies. Overall, dental chairside assistants experienced a higher incidence of injuries than students both on a per worker and per time basis. Of the injuries with a low risk of cross‐infection, burns and scalds from sterilizing equipment, and eye injuries in laboratories were the most common. This emphasizes the importance of wearing appropriate protective equipment in areas outside the treatment zone, and the need for signage and education. Common causes of sharps injuries were burs left in handpieces, two‐handed needle recapping, and cleaning of probes in the sterilizing room. Changes to techniques and equipment would prevent such incidents. A range of factors which contribute to the calculation of indirect costs following injuries in the dental workplace are identified.

Growth factors play an important role in the regulation of cell growth, division and differentiation. In this study the distribution and regulation of insulin-like growth factor-I (IGF-I) in the continuously erupting rat incisor was determined by immunohistochemistry. Results were evaluated both visually and with a computer-based image analysis system. The distribution and intensity of IGF-I immunoreactivity varied with developmental stage of the rat incisor. Strong IGF-I immunoreactivity was observed in differentiating odontoblasts and ameloblasts. The most intense immunoreactivity was observed in secretory ameloblasts, secretory odontoblasts and in maturation ameloblasts. Staining was weak or absent in post-secretory ameloblasts but persisted in post-secretory odontoblasts. Weak to moderate immunoreactivity was also seen in cells of the stratum intermedium and in the reduced enamel epithelium. Surrounding alveolar bone showed strong IGF-I immunoreactivity in osteoblasts and in the stratum basale and stratum spinosum of the adjacent labial gingival epithelium. In order to assess the role of GH in IGF-I expression, GH (65μg/100 g bw) was administered for six days to dwarf GH deficient rats, producing a significant increase in body weight (P < 0.01). Measurements at different stages of odontogenesis showed that the staining intensity of secretory ameloblasts (P<0.01) and maturation ameloblasts (P<0.001) was significantly different between untreated and treated animals. These results indicate that IGF-I is present in cell populations of the enamel organ of the rat incisor found previously to exhibit growth hormone receptors, and that expression of IGF is GH dependent. These findings support the concept that paracrine or autocrine synthesis of IGF-I mediates the effects of growth hormone on the growth and secretory function of cells forming the rat mandibular incisor.

Cyclosporin‐A (CsA)‐induced gingival enlargementhas been reported in a small number of cases but may involve up to one third of all patients taking CsA. The present study reports a case of CsA‐induced gingival enlargement during suppressive therapy for myasthenia gravis. Gingival tissues were examined histologically, histochemically, and immunohistologically. The basic tissue response seemed to be a dental plaque‐ and traumainduced fibroblastic response characterized by large aggregations of plasma cells, macrophages and helper T lymphocytes. The reactive areas rapidly matured into noninflamed fibrocytic tissue. The suppressive effect of CsA appears responsible for removal of sectors of the normal immune response and, in combination with an elevated number of macrophages, may be instrumental in initiating a fibrous hyperplastic response.

Sodium molybdate affected the stability of vervet monkey (Cercopithecus aethiops pygerythrus) uterine estrogen (ER) and progesterone (PR) receptors. Yields of receptors were invariably higher (20 - 40 %) when cytosols were prepared in the presence of 10mM sodium molybdate. No changes were observed in the binding affinities for the natural ligands as reflected in dissociation at 0°C and 20°C was not affected in the presence or absence of molybdate. Stability studies at 37°C indicated both receptors to be more resistant to inactivation in the presence of molybdate. Dissociation of ER and PR was biphasic, indicating the existence of slow (SDC), as well as fast dissociating (FDC) complexes. Rate constants of dissociation were significantly affected by the presence of sodium molybdate Although no significant changes in the sedimentation coefficeints were observed, marked differences in the actual gradient profiles could be illustrated in the presence or absence of sodium molybdate. Observed effects could only be partially reversed in sedimentation dialysis experiments. Proteolytic inhibitors phenlymethylsulfonylfluoride (PMSF) and leupeptin had no inhibitive effect on the molybdate stabilization of ER and PR.

Intravenous inoculation of Streptobacillus moniliformis into mice resulted in an infection in which the predominant feature was progressive polyarthritis that rendered some joints immobile within 6 months. No migration of arthritis from joint to joint or remission and exacerbation were apparent. Viable organisms were apparently removed by the host from blood, liver, and spleen within 28 days post inoculation but persisted in joints for approximately 6 months in some animals. Specific antibody was detectable by complement fixation 7 days post-inoculation and persisted throughout the course of the disease. The inflammatory responses, which was initiated by the appearance of neutrophils in the joint space within 24 h of inoculation, culminated in obliteration of the joint space by fibrosis and exostosis.

The total content of 17-beta estradiol and progesterone receptors in human uterine leiomyoma and normal myometrium in a Caucasian population was determined. Estrogen receptor concentrations in leiomyoma and myometrium were not significantly different (p = 0.1401). The concentration of progesterone receptors in leiomyoma was higher than in myometrium (p = 0.0303).Negroid and Caucasian ethnic groups did not differ with respect to estrogen (p = 0.7040) or progesterone (p =0.8494) receptor concentrations in leiomyoma, but estrogen (p < 0.005) and progesterone (p < 0.005) receptor concentrations in normal myometrium were significantly higher in Caucasian than in negroid patients.Leiomyoma in negroid and Caucasian patients appears to be histologically similar, but the biochemical pathway of its pathogenesis seems to differ. Genetic predisposition probably acts as an initiation factor in the myometrium of both ethnic groups, then estrogen receptor levels in negroids and alterations in steroid metabolism in Caucasians promote the growth of leiomyoma.

The group I (Der p 1) allergen of Dermatophagoides pteronyssinus (house dust mite, HDM) contains several T helper (Th) epitopes recognized by C57BL/6 mice, with the peptide (111-139) containing a dominant MHC class II-restricted epitope (113-127). Since CD8+ T cells are thought to play a role in the regulation of allergic disease, we examined the Der p 1 sequence for potential MHC class I-binding motifs and observed that residues 111-119 (FGISNYCQI) contain motifs for H-2Db and Kb. Furthermore, immunization of C57BL/6 mice with unadjuvanted Ty virus-like particles (VLP) carrying Der p 1 (111-139), a method known to induce murine cytotoxic T lymphocyte (CTL) responses, primed Der p 1 (111-119)-specific Db-restricted CTL which produce high levels of IFN-gamma and low levels of IL-5 and IL-6 in vitro (T1-type CTL). VLP carrying the minimal epitope (FGISNYCQI) also induced a CTL response following immunization without adjuvant by various routes. Der p 1 (111-139)-VLP adjuvanted with alum did not prime CTL in C57BL/6 mice but were found to prime Th1-type CD4+ T cells that recognize the overlapping peptide (113-127) and native protein. The ability to successfully predict allergen-specific CD8+ T cell epitopes and prime CD8+ and/or CD4+ T cell responses provides an opportunity to dissect the relative roles of these T cells in the regulation of allergic responses and may offer therapeutic potential for reprogramming Th2-type allergic responses.

The content of cytoplasmic 17β oestradiol and progesterone receptors in human uterine leiomyoma and normal myometrium in the Negroid population was determined. Eighteen women of reproductive age, at various stages of the menstrual cycle, were included in the study. The serum oestrogen and progesterone concentrations were also measured. This is the first report in the literature in which oestrogen and progesterone receptors in leiomyoma are significantly higher than in normal myometrium (P=0·0002). The steroid dependence of the growth of leiomyomas may be related to the steroid receptor level. The presence of persistently high concentrations of oestrogen and progesterone receptors in leiomyoma should be helpful in the treatment of this benign tumour.

Insulin-like growth factor-I(IGF-I) has both metabolic and growth-promoting activities in many cell and tissue types. Although IGF-I is present in serum, it is also thought to have important autocrine and paracrine functions. Immunohistochemistry for IGF-I and its receptor have shown that IGF-I is synthesised locally by the tooth forming cells which exhibit both the IGF-I and the growth hormone receptors. This concept required to be tested by in situ hybridization. Using a digoxigenin-labelled synthetic oligodeoxyribonucleotide probe for IGF-I, we investigated the distribution of IGF-I mRNA in the continuously erupting rat incisor by in situ hybridization. The distribution and intensity of the hybridization signal varied with the developmental stage of the rat incisor. The cells of the apical loop expressed a positive hybridization signal, but the earliest polarised odontoblasts and pre-ameloblasts did not show any positive signal. The onset of enamel secretion was accompanied by a strong hybridization signal in the secretory ameloblasts as well as the odontoblasts. Maturation ameloblasts also demonstrated IGF-I message in their cytoplasm as well as their nuclei. The cells of the pulp and the dental follicle were consistently negative. However, in the adjacent alveolar bone, the signal was high in the osteoblasts and osteoclasts. These findings support the notion of paracrine or autocrine function for IGF-I in tooth development.

Ultraturrax- and Nagarse-released populations of mitochondria were characterized with respect to their Ca2+-uptake activities (i) by means of the indirect polarographic technique and (ii) directly by the 45Ca Ruthenium Red-quench method of Reed & Bygrave [(1974) Biochem. J. 140, 143-155]. The denervated-muscle subsarcolemmal and intermyofibrillar mitochondrial fractions displayed markedly decreased rates and capacities for Ca2+ uptake compared with their respective controls. The implications of these findings with respect to the process of cell necrosis are discussed.

Denervation of rat skeletal muscle produces after 14 days a decrease in Ca2+ uptake of a heterogeneous population of sarcoplasmic-reticulum vesicles, when measured in the presence of oxalate. The Mg2+-dependent ATPase (Ca2+-independent) activity increased after the same period and the Ca2+ + Mg2+-dependent ATPase activity decreased. Concomitant with these changes, there was an increase in vesicle size and calcium content. The observations are discussed in terms of changes in altered membrane structure, manifested in the shift of the equilibrium of the ATPase from an enzyme involved in calcium transport to a phosphoenzyme giving rise to an increase in the Mg2+-dependent ATPase activity.

Experiments are reported showing some slight protective capacity of guinea pig antimouse leukemic tissue serum to protect the AKR mouse against the BW5147 tumor, when the serum is first adsorbed to remove precipitating antibody for the tissue cell antigens. The degree of protection is slight, and all mice eventually died of the tumor development. Results of one injection of tumor tissue – oleic acid emulsion show up to 46% survival of the immunized mice following challenge injections of active tumor preparation. No protection is seen after a similar injection of tumor material which had remained frozen for several months. Repeated injection of frozen tumor tissue produced leukemic tumor development in test mice, indicating that this material retains some activity under these conditions, and that sufficient immunity cannot be produced by these injections to protect against the disease.

Experiments are reported showing some slight protective capacity of guinea pig antimouse leukemic tissue serum to protect the AKR mouse against the BW5147 tumor, when the serum is first adsorbed to remove precipitating antibody for the tissue cell antigens. The degree of protection is slight, and all mice eventually died of the tumor development. Results of one injection of tumor tissue – oleic acid emulsion show up to 46% survival of the immunized mice following challenge injections of active tumor preparation. No protection is seen after a similar injection of tumor material which had remained frozen for several months. Repeated injection of frozen tumor tissue produced leukemic tumor development in test mice, indicating that this material retains some activity under these conditions, and that sufficient immunity cannot be produced by these injections to protect against the disease.

Five mutagens were used to induce mutants of Candida albicans.Ultraviolet light, N-nitroso-N′-methyl-N-nitrosoguanidine, and N-nitroso-N-methylurethane were effective mutagens which induced stable auxotrophs. N-nitroso-N-methylurethane produced the largest number and variety of mutants. Nitrous acid and hydroxylamine were ineffective as mutagens although they killed C. albicans.All mutagenic agents employed induced colonial variants, especially small colony forms. The morphology, physiology, and virulence of one methionine and two adenine auxotrophs was compared to that of the prototroph. The auxotrophs exhibited yeast-like morphology in complex media and had sugar fermentation patterns typical of C. albicans, and all were agglutinated by C. albicansantiserum. Chlamydospore production was absent in the nonpigmented adenine mutant, and the chlamydospores produced by the methionine auxotroph were distorted. Germ tubes were formed in human serum by the auxotrophs and prototroph. Virulence for mice was retained by all auxotrophs but generally at a reduced level. The methionine auxotroph, only slightly less virulent than the prototroph, was more virulent than a pigmented adenine mutant and a practically avirulent nonpigmented adenine auxotroph.

Several variables of host and parasite, relating to the establishment of the chronic Streptobacillus moniliformis-induced arthritis, were studied. Results from these studies indicated (i) that intravenous inoculation of the organism produced a progressive bacteremia and a polyarthritis, whereas subcutaneous inoculation into the top of the back foot produced an intermittent bacteremia and arthritis only in that foot, (ii) that serum-broth-grown cells were more virulent than serum-agar-grown cells, (iii) that young animals were more susceptible to infection than old, and (iv) that the organism apparently had a predilection for joints. It was also determined that the leukocyte and antibody responses of mice to infection were minimal with a slight neutrophilia and a maximum antibody titer of 1:640 detected after infection. Measurements of the effectiveness of antibody and leukocytes in prevention or resolution of infection indicated (i) that the presence of homologous antibody prior to infection prolonged the incubation period for development of the lesion, (ii) that the opsonic index was 1.2 to 1.4, and (iii) that the organism was apparently resistant to destruction by in vitro phagocytosis and actually increased in number in the presence of phagocytes. It was concluded that these represented some of the prime factors contributing to the establishment of the infection and its chronicity.

We have investigated the possible role of the interleukin-1 receptor antagonist (IL-1ra) in the attenuated fever response in the newborn. Umbilical cord blood was collected from normal full-term infants (n=12), and venous blood was obtained from afebrile, non-pregnant adults, of both genders (n=12) and women in late pregnancy (n=12). Plasma IL-1ra, and IL-1ra produced in vitro by peripheral blood monocytes stimulated with IL-1a or LPS, were assayed by ELISA. Significantly higher concentrations of IL-1ra (P<0.01, t test) were found in umbilical cord plasma than in plasma of non-pregnant adults. Furthermore concentrations of IL-1ra in the plasma of women in late pregnancy were significantly higher than in the plasma of neonates and non-pregnant adults (P<0.01, Mann-Whitney rank-sum test). Neonatal monocytes failed to produce significant amounts of IL-1ra upon stimulation in vitro. The monocytes of pregnant women produced much higher concentrations of IL-1ra than the monocytes of non-pregnant adults (P<0.01 Mann-Whitney rank-sum test). We speculate that IL-1ra may attenuate the febrile response to Gram-negative pyrogens in women in late pregnancy, and by crossing the placenta, also in the newborn.

DEPANCREATIZED baboons, deprived of insulin for 4 days, develop a lipæmia and a fatty liver, which may contain 34 per cent of fat when estimated on a wet-weight basis1,2. The lipæmia in diabetic rats has generally been attributed to mobilization of fat from the depots. In the baboon, the severity of the lipæmia and the degree of fat accumulation in the liver, particularly in young animals with poorly developed fat depots, suggested that the fat was not mobilized only from the depots, and this warranted a re-investigation of the origin of the fat in the liver and in the plasma. In this communication it is proposed to report on the incorporation of 2-14C sodium pyruvate into the glyceride glycerol in a normal baboon and in depancreatized baboons either receiving insulin or deprived of insulin.