Emerging Salmonella Enteritidis anaerogenic phage type 14b: Outbreak in Norwegian, Swedish and Finnish travellers returning from Greece.

In July 2001, the Norwegian Institute of Public Health (Folkehelseinstituttet, FHI) reported a cluster of Salmonella Enteritidis of phage type 14b infections in Norwegian travellers returning from Greece. An increase in the same uncommon phage type was also registered in Sweden and Finland at the same time. Cases of S. Enteritidis PT 14b in patients returning from Greece were reported in these three Nordic countries in 2001 (303 cases), 2002 (164 cases) and 2003 (199 cases). Case-control studies performed in 2001 in Norway and Sweden indicated that consumption of chicken was associated with illness. In 2002 and 2003, continuing case reports indicated that this uncommon phage type had probably become established in the Greek food chain. Tour operators were informed and contacts were made with Greek public health authorities. Because place of infection is not systematically included in most Salmonella notification systems, the S. Enteritidis phage type 14b outbreak reported here may represent only part of a larger outbreak among travellers visiting Greece. Infections are often reported only in the tourists' home countries and public health authorities in the tourist destinations may not be aware of the problem. Further collaboration between national institutes of public health in Europe is needed to detect outbreaks occurring among tourists.

Emerging Salmonella Enteritidis anaerogenic phage type 14b: outbreak in Norwegian, Swedish and Finnish travellers returning from Greece.

In July 2001, the Norwegian Institute of Public Health (Folkehelseinstituttet, FHI) reported a cluster of Salmonella Enteritidis of phage type 14b infections in Norwegian travellers returning from Greece. An increase in the same uncommon phage type was also registered in Sweden and Finland at the same time. Cases of S. Enteritidis PT 14b in patients returning from Greece were reported in these three Nordic countries in 2001 (303 cases), 2002 (164 cases) and 2003 (199 cases). Case-control studies performed in 2001 in Norway and Sweden indicated that consumption of chicken was associated with illness. In 2002 and 2003, continuing case reports indicated that this uncommon phage type had probably become established in the Greek food chain. Tour operators were informed and contacts were made with Greek public health authorities. Because place of infection is not systematically included in most Salmonella notification systems, the S. Enteritidis phage type 14b outbreak reported here may represent only part of a larger outbreak among travellers visiting Greece. Infections are often reported only in the tourists' home countries and public health authorities in the tourist destinations may not be aware of the problem. Further collaboration between national institutes of public health in Europe is needed to detect outbreaks occurring among tourists.

Risk factors associated with typhoid fever in Son La province, northern Vietnam.

Between July and December 2002, we undertook a hospital-based case-control study to identify risk factors associated with typhoid fever in Son La province, northern Vietnam. Among 617 suspected cases, 90 cases of typhoid fever were confirmed by blood or stool culture. One hundred and eighty controls (neighbours of typhoid cases matched for gender and age) were chosen. Participants were interviewed at home using a standardized questionnaire. Seventy-five per cent of cases were aged 10-44 years. No cases in patients aged less than 5 years were recorded in this study. In a conditional logistic regression analysis recent contact with a typhoid patient (OR = 3.3, 95% CI 1.7-6.2, P < 0.001), no education (OR = 2.0, 95% CI 1.0-3.7, P = 0.03) and drinking untreated water (OR = 3.9, 95% CI 2.0-7.5, P < 0.001) were independently associated with typhoid fever. Improving quality of drinking water must be a priority and health education strategies targeted at individuals with no schooling, and contacts of patients, would be expected to decrease the burden of typhoid fever.

Quantitative analysis of cytosolic free calcium oscillations in neutrophils by mathematical modelling.

Mathematical models are often used to elucidate mechanisms behind cytosolic Ca2+ oscillations. We have evaluated the use of mathematical modelling to analyse and quantify Ca2+ signal patterns, in single, adherent human neutrophils (PMN) after stimulation by the bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP). The cells were loaded with Fura-2 and fluctuations in cytosolic Ca2+ recorded with a video based digital imaging system. A new indirect intracellular calibration method was introduced to avoid the uncertainty in obtaining an equilibrium between the extracellular and intracellular calcium concentrations. Two different approaches to mathematical modelling were used. First, we applied a sensitivity analysis with a two-pool model by assuming an optimal situation using reliable a priori estimates of all structural parameters (e.g. Hill coefficients and dissociation constants). We found that the a priori estimates of the other 5 more variable parameters must lie within the range of 25-400% of the postulated true parameter values to be reliable in a parameter estimation method. Small changes (less than 5%) in those variable parameter values induced very different types of signal patterns which may have some relevance in evaluating a possible functional significance to the oscillatory signals. Second, we employed a one-pool, non oscillatory model integrated with a power spectrum method as a tool to quantify the dose dependency between fMLP (1-1000 nM) and parameters describing the biphasic process of calcium signalling and parameters describing only the oscillatory components. We conclude that the frequency of the observed oscillations assembled around one characteristic frequency independent of fMLP concentration, and sinusoidal oscillations were observed most frequently in PMN stimulated to a moderate peak [Ca2+]i level.

Synchronized Ca2+ oscillations induced in Madin Darby canine kidney cells by bradykinin and thrombin but not by ATP.

In an earlier report, we described synchronous Ca2+ oscillations in globally stimulated, subconfluent MDCK cells [Røttingen J-A, Enden T., Camerer E., Iversen J-G., Prydz H. Binding of human factor VIIa to tissue factor induces cytosolic Ca2+ signals in J82 cells, transfected COS-1 cells, Madin-Darby canine kidney cells and in human endothelial cells induced to synthesize tissue factor. J Biol Chem 1995; 270: 4650-4660]. In order to elucidate the mechanisms behind these oscillations, we have analyzed the fluctuations in cytosolic Ca2+ in single, Fura-2 loaded, MDCK cells grown to subconfluence, after stimulation with bradykinin, thrombin and ATP. All three agonists gave rise to an initial Ca2+ spike followed by oscillations or transients. Both the initial and subsequent spikes appeared to be due mainly to release of Ca2+ from internal stores, since they remained after Ca2+ influx was impeded by either La3+ or by chelation of extracellular Ca2+ with EGTA. The secondary spikes were apparently synchronized when the cells were (permanently and globally) stimulated with bradykinin or thrombin, but each cell seemed to oscillate independently when stimulated in the same way with ATP. Synchronized secondary spikes arose with a constant frequency and amplitude, independent of agonist concentration in contrast to most Ca2+ oscillations observed. Pretreatment of the cells with octanol to block gap junctions, or with EGTA or La3+ to inhibit Ca2+ influx, abolished the synchronization induced by bradykinin or thrombin. We observed that in the MDCK cell layer there are some "pacemaker' cells and hypothesize that these have a higher sensitivity for the agonists than their neighboring cells. From these pacemakers, an intercellular Ca2+ wave can be seen to spread to adjacent cells in the presence of intact gap junctions, thereby initiating concurrent transients in all cells. The Ca2+ wave is amplified by release from internal stores, probably owing to the bell-shaped Ca2+ activation curve of the IP3 receptor and by subsequent Ca2+ influx through Ca2+ release activated channels.

Rocuronium and anaphylaxis--a statistical challenge.

Drug induced anaphylaxis is frequently attributed to the use of muscle relaxants during anaesthesia. Recently The Norwegian Medicines Agency recommended that rocuronium bromide (Esmeron) be withdrawn from routine practice due to frequent reports of anaphylaxis. Over a period of two and a half years approximately 150,000 patients received rocuronium as part of their anaesthesia. In this period the Norwegian drug authorities received 29 reports of anaphylaxis or anaphylactoid reactions in patients treated with rocuronium. This is in stark contrast to the situation in other Nordic countries where a total of only seven cases of anaphylaxis in approximately 800,000 patients treated with rocuronium had been recorded by December 2000. This situation highlights the many potential problems of the surveillance of adverse drug reactions: reporting bias may lead to an over-estimate of the risk of one drug compared to another, and the possibility of under-reporting of adverse events (due to a weak reporting culture) further limit the validity of such comparisons. The surveillance of adverse drug reactions also represents a statistical challenge. While adverse event reports may help us to estimate the anaphylaxis rate we need to appreciate the uncertainty of such estimates. Adverse reactions are rare, random, and mostly independent events, resulting from the successive exposure of patients to a low risk intervention. The frequency distribution of adverse events will therefore conform to that of a Poisson process. The resulting Poisson distribution may inform us about the variability of adverse event data. An understanding of these methodological problems and statistical challenges will allow anaesthesiologists to make informed decisions concerning the use of muscle relaxants and other drugs associated with severe adverse reactions.

[Environmental pollutants with hormonal effects. Is estrogen theory a good model?]. / Miljøgifter med hormonelle effekter. Er østrogenteorien en god forklaringsmodell?

Lately, a theory on possible oestrogenic effects of environmental contaminants like PCB, dioxin and some pesticides, has caused much concern. The "oestrogen theory" states that persistent, bioaccumulating chemicals affect foetal development by acting like oestrogens. This results in permanent changes, of the reproductive organs in particular, and leads to reduced reproductive success. The theory is based to a large degree on reports on animals from the Great Lakes region in North America, alligators from Florida and fish from rivers in Great Britain. Now that a decline in human semen quality over the last 50 years has been reported, the question has been raised as to whether this too may be a result of environmental oestrogens. The higher incidence of other diseases like hypospadia, cryptorchidism and testicular cancer also indicates that something may be affecting the reproductive health of the male. Whether the higher incidence of endometriosis and breast cancer can be explained by the hypothesis is questioned. That several environmental contaminants have oestrogenic effects, has been documented. Recent studies have shown that the contaminants have more general endocrine-disrupting effects, thereby indicating that the oestrogen model is too simple. It is a dilemma for environmental medicine whether the present knowledge gives sufficient reason to apply precautionary principle and demand specific regulations.

[Cecal volvulus as a complication in Cornelia de Lange syndrome. A case report and literature review]. / Cøkal volvulus som komplikasjon ved Cornelia de Langes syndrom. En kasuistikk med gjennomgang av litteraturen.

Colonic volvulus in children is a rare, but serious and important differential diagnosis in acute abdominal illness. Our patient with Cornelia de Lange's syndrome, was admitted with an acute onset of abdominal pain and in a critical condition. Explorative laparotomy revealed a caecal volvulus with necrosis of the distal ileum, caecum and proximal colon. The syndrome is characterized by typical facial expression, both growth and mental retardation, and various gastrointestinal and cardiac anomalies. Predisposing factors contributing to volvulus in this syndrome are mental retardation and a higher incidence of malrotation and nonfixation of the caecum and ascending colon. The parents of children with Cornelia de Lange's syndrome should therefore be counselled so that they are able to provide essential information in the event of their children experiencing acute illness.

A systematic review of the epidemiologic interactions between classic sexually transmitted diseases and HIV: how much really is known?

BACKGROUND: Many studies have explored the role of "classic" sexually transmitted diseases (STDs) in determining the pattern of HIV epidemics. However, the many different STDs may contribute in different ways, at different magnitudes. GOAL: To review available studies on the bidirectional interactions of HIV and STDs to explore the extent of current knowledge on the different influences of the varied STDs in heterosexual HIV epidemics. METHODS: Longitudinal studies on susceptibility and controlled studies on infectiousness and duration of disease identified on electronic databases through reference lists and citation indices up to the end of 1999 were systematically reviewed, including meta-analyses assessing the influence of STDs on susceptibility to HIV. RESULTS: Studies have a clear publication bias with a significant result that hinders robust interpretation. However, genital ulcerative disease appears to have a greater impact than nonulcerative disease, and men are more affected than women by the effects of STDs on susceptibility to HIV. There is evidence that STDs increase the infectiousness of HIV from men to women, whereas the evidence is more equivocal for the infectiousness of women. Few studies identify the impact of different STDs, and there is a marked lack of studies investigating the impact of HIV infection on the transmission of other STDs. CONCLUSIONS: A large body of work has measured the association between STDs and HIV. However, publication bias and gaps in the focus of studies mean that a detailed, quantitative understanding of the interaction requires much more attention.

Waterborne outbreak of gastroenteritis in a religious summer camp in Norway, 2002.

In July 2002 an outbreak of acute gastroenteritis occurred in a camp facility in western Norway during a 10-day seminar, with around 300 guests staying overnight and several day-time visitors. Environmental and epidemiological investigations were conducted to identify and eliminate the source of the outbreak, prevent further transmission and describe the impact of the outbreak. Of 205 respondents, 134 reported illness (attack rate, 65%). Multivariate analysis showed drinking water and taking showers at the camp-site to be significant risk factors. Secondary person-to-person spread among visitors or outside of the camp was found. Norovirus was identified in 8 out of the 10 stool samples analysed. Indicators of faecal contamination were found in samples from the private untreated water supply, but norovirus could not be identified. This outbreak investigation illustrates the importance of norovirus as a cause of waterborne illness and the additional exacerbation through person-to-person transmission in closed settings. Since aerosol transmission through showering contributed to the spread, intensified hygienic procedures such as isolation of cases and boiling of water may not be sufficient to terminate outbreaks with norovirus.

Definition and estimation of an actual reproduction number describing past infectious disease transmission: application to HIV epidemics among homosexual men in Denmark, Norway and Sweden.

Prevalence and incidence measures are the common way to describe epidemics. The reproduction number supplies information on the potential for growth or decline of an epidemic. We define an actual reproduction number for infectious disease transmission that has taken place. An estimator is suggested, based on the number of new infections observed in a given time-interval, the number of those infected at the start of the interval, and the length of the infectious period. That estimator is applied to HIV among men having sex with other men over the period, 1977-1995, in Scandinavia. The actual reproduction number was estimated with acceptable certainty from the period, 1981-1982, yielding a value of 15 secondary cases. A value of less than one secondary case was assessed for the period, 1988-1995, in Denmark and Sweden. The actual reproduction number gives us some additional understanding of the dynamics of epidemics, compared with prevalence and incidence curves.

Phagocytic dendritic cells from myelomas activate tumor-specific T cells at a single cell level.

Antigen-presenting cells (APCs) from subcutaneous mouse MOPC315 plasmacytoma phagocytosed immunoglobulin G-coated magnetic beads, enabling efficient isolation within 2 hours by magnetic separation (APC-MB). Cell morphology was heterogeneous, with some of the cells having dendrites. The surface phenotype of purified tumor APCs-MB was CD11b(+), CD11c(+), CD40(+), CD80(+), CD86(+), and MHC class II(+). Tumor APCs-MB expressed messenger RNA for fractalkine and ABCD-1 chemokines, and for CC-type chemokine receptors CCR5 and CCR7, indicating the presence of mature dendritic cells (DCs). Visualized at a single cell level within 4 hours after disruption of the tumor, APCs-MB induced rapid Ca(++) mobilization in MHC class II-restricted tumor idiotype (Id)-specific cloned CD4(+) T cells. In long-term assays, tumor APCs-MB induced proliferation of naive T cells from Id-specific T-cell receptor transgenic mice. The results suggest that tumor APCs-MB represent a heterogeneous cell population that includes myeloid-derived DCs of various stages of maturation. A considerable fraction (> or = 15%) of DCs is spontaneously primed with tumor-specific antigen.

Coagulation factors VII and X induce Ca2+ oscillations in Madin-Darby canine kidney cells only when proteolytically active.

We have recently reported that the activated serine protease and blood coagulation Factor VII (FVIIa) can induce Ca2+ oscillations in Madin-Darby canine kidney cells. We now demonstrate a similar response by Madin-Darby canine kidney cells to the active coagulation Factor X (FXa), which is also a serine protease and a substrate of the tissue factor (TF).FVIIa complex in the initiation of the coagulation cascade. The phosphatidyl inositol-specific phospholipase C inhibitor U73122 inhibited the signals elicited by both FVIIa and FXa. Lack of sensibility to the tyrosine kinase inhibitors herbimycin A, genistein, and the tyrphostin AG18 and discordance between TF expression and FVIIa responsiveness argued against TF acting as a cytokine-like receptor, with tyrosine kinase-mediated activation by FVIIa. As demonstrated using the protease inhibitor benzamidine and by specific active site inhibition with 1,5-dansyl-Glu-Gly-Arg chloromethyl ketone, both FVIIa and FXa lost their ability to elicit a calcium response when devoid of their proteolytic activity. Consistent with this, the native (zymogen) form of Factor X did not induce Ca2+ transients. Homologous but not heterologous inhibition of FVIIa- and FXa-evoked Ca2+ signals by 1,5-dansyl-Glu-Gly-Arg chloromethyl ketone-inactivated FVIIa and FXa suggested that each factor had its own specific cell surface anchoring receptor. The two coagulation factors did not show homologous desensitization as seen for thrombin stimulation. Studies with hirudin excluded involvement of the established activation pathway through thrombin itself. Lack of desensitization of the response to FVIIa or FXa by thrombin ruled out any involvement of proteinase activated receptor-1 (PAR-1), the thrombin receptor. We speculate that FXa and FVIIa may work via a receptor (possibly common) analogous to PAR-1 or its functional homologue PAR-2. Although TF is essential for the FVIIa-induced signaling event, its role in the phosphatidyl inositol-specific phospholipase C-mediated Ca2+ signal may be in anchoring FVIIa to the cell surface rather than in transmembrane signal mediation.

[Medical research at Norwegian universities]. / Medisinsk forskning ved norske universiteter.

This study shows that Norwegian medical research suffers from lack of both public funds and recruitment, as well as being affected by the following major factors. Norway uses less of its GNP on R&D than other Western countries and less than the OECD average. Medical research in particular receives less financial support than in any of the other Nordic countries. Norwegian medical researchers publish less material and are cited less often than their colleagues in comparable countries. More than half of the medically trained scientific staff in Norway's four medical faculties will retire during the next decade and today there are many vacant positions in academic medicine because there are not enough competent applicants to fill them. The percentage of M.D.s among professors and lecturers has fallen, and a continued decline in preclinical and laboratory medicine and in public health is predicted. This percentage has also decreased among Ph.D. students, while the age at which medical doctors dissertate has increased and is higher than for other Ph.D.s. The number of medical students doing research has fallen in recent years, and the number of doctoral theses has not increased as much in medicine as in other fields. There are significant differences between the salaries paid in medical science and those paid in clinical medicine. Lack of resources and low salaries keep doctors from pursuing a career in academic medicine. In conclusion, if Norway is to be visible in the field of international medical science, this negative trend must be reversed and medical research and academic medicine revitalised.

Binding of human factor VIIa to tissue factor induces cytosolic Ca2+ signals in J82 cells, transfected COS-1 cells, Madin-Darby canine kidney cells and in human endothelial cells induced to synthesize tissue factor.

Tissue factor (TF) is the most potent trigger of blood clotting known. It activates factor VII (FVII) thereby initiating a cascade of proteolytic reactions resulting in thrombin production. The cloning of TF revealed its structural characteristics to be those of a receptor related to the class 2 cytokine receptor superfamily, but until now no intracellular signal has been discovered related to binding of the ligand (FVIIa) to the putative receptor. We have studied possible intracellular signaling effects of the FVIIa-TF interaction by measuring cytosolic free Ca2+ in single fura-2-loaded cells and found that 200 nM FVIIa caused Ca2+ transients in about 30% of human umbilical vein endothelial cells treated with interleukin-1 beta to express TF, compared to below 5% in uninduced cells. A gradual increase of the basal Ca2+ level was also caused by binding of FVIIa. In the human bladder carcinoma cell line J82, which has a high constitutive TF activity, similar results were found. An antibody neutralizing TF activity decreased the response rate to control levels. COS-1 cells which do not make TF did not respond to FVIIa as opposed to COS-1 cells expressing TF after transfection with a human TF cDNA construct. The canine kidney cell line MDCK, a constitutive TF producer, responded especially well; up to 100% of the cells examined showed Ca2+ oscillations which were dose dependent with regard to frequency, latency, maximal amplitude, and recruitment of responding cells. The frequency was reduced by inhibition of Ca2+ influx with 100 microM LaCl3. In confluent MDCK cells the Ca2+ oscillations were synchronous, constituting the first evidence of a synchronous cytosolic Ca2+ oscillator generated by global application of agonist. Thus, TF mediates a cytosolic Ca2+ signal upon interaction with its ligand FVIIa, thereby suggesting a more complex biological role for TF.

Association between environmental risk factors and campylobacter infections in Sweden.

Campylobacter sp. is the most common cause of acute bacterial gastroenteritis in Sweden and the incidence has been increasing. Case-control studies to identify risk factors have been conducted in several countries, but much remains unexplained. The geographical distribution of campylobacter infections varies substantially, and many environmental factors may influence the observed pattern. Geographical Information Systems (GIS) offer an opportunity to use routinely available surveillance data to explore associations between potential environmental risk factors showing a geographical pattern and disease incidence, complementing traditional approaches for investigating risk factors for disease. We investigated associations between campylobacter incidence and environmental factors related to water and livestock in Sweden. Poisson regression was used to estimate the strength of the associations. Positive associations were found between campylobacter incidence and average water-pipe length per person, ruminant density, and a negative association with the percentage of the population receiving water from a public water supply. This indicates that drinking water and contamination from livestock may be important factors in explaining sporadic human campylobacteriosis in Sweden, and that contamination occurring in the water distribution system might be more important than previously considered.

Global, synchronous oscillations in cytosolic calcium and adherence in bradykinin-stimulated Madin-Darby canine kidney cells.

AIMS AND METHODS: Intercellular Ca2+ oscillations are a universal mode of signalling in both excitable and non-excitable cells. Here, we study the relationship between Ca2+ signalling and coherent changes in adhesion properties by measuring the transepithelial impedance across bradykinin-stimulated Madin-Darby canine kidney (MDCK) cell layers grown on a microelectrode. During hormone stimulation, the impedance is found to oscillate, reflecting that the cells undergo morphological/adhesive alterations with high spatio-temporal organization. The experiments are supplemented with parallel, digital imaging fluorescence microscopy of bradykinin-induced single-cell Ca2+ oscillations. RESULTS: In agreement with previous experiments, MDCK cells are found to elicit synchronous, multicellular Ca2+ oscillations in response to hormone stimulus. The periods of the Ca2+ oscillations and the electrical fluctuations are found to coincide. Further, blocking of gap junctions by 18alpha-glycyrrhetinic acid causes a loss of synchrony in Ca2+ signals and inhibition of impedance oscillations, emphasizing the importance of gap junctions in the signal transduction process. CONCLUSION: Based on these observations it is concluded that the co-ordinated adhesive changes in MDCK cells are a direct consequence of synchronized Ca2+ oscillations. Calcium signalling represents an efficient way of organizing physiological responses in a tissue. A possible functional implication of the structural changes might be to modulate transportation of various substances across the cell sheet.

On the mechanisms of the growth-promoting effect of prostaglandins in hepatocytes: the relationship between stimulation of DNA synthesis and signaling mediated by adenylyl cyclase and phosphoinositide-specific phospholipase C.

While many observations indicate that prostaglandins may act as positive regulators of hepatocyte proliferation, the underlying mechanisms are not known. We have examined some of the signal pathways in the growth response induced by prostaglandins in hepatocytes, with particular focus on adenylyl cyclase and phosphoinositide-specific phospholipase C. Adult rat hepatocytes were cultured as primary monolayers in serum-free medium in the presence of EGF and insulin. PGE2 or PGF2 alpha (added 0-3 h after plating) enhanced the incorporation of [3H]-thymidine into DNA (measured at 50 h); at 100 microM the stimulation was about threefold PGI2 and PGD2 also showed significant but smaller stimulatory effects. No significant increase in the level of cyclic AMP (cAMP) was detected in response to any of the prostaglandins. Low concentrations of glucagon (0.1-10 nM), a potent activator of hepatic adenylyl cyclase, or 8-bromo-cAMP (0.1-10 microM) enhanced the DNA synthesis. When 8-bromo-cAMP was used in maximally effective concentrations, no further stimulation was obtained by combining it with glucagon, whereas the effects of PGE2 and 8-bromo-cAMP were completely additive. All the prostaglandins also showed additivity with the effect of glucagon on the DNA synthesis. PGE2, PGF2 alpha, PGI2, and PGD2 increased intracellular inositol-1,4,5-trisphosphate (InsP3), with a relative order of efficacy roughly corresponding to their activity as stimulators of DNA synthesis. Increases in cytosolic free Ca2+, as measured in single cells, were elicited in a majority of the hepatocytes by all these prostaglandins at 1 microM. Supramaximal concentrations of vasopressin, a strong activator of phospholipase C in hepatocytes, acted additively with PGE2 on the DNA synthesis. Pretreatment of the hepatocytes with a concentration of pertussis toxin that prevented the inhibitory effect of PGE2 on glucagon-induced cAMP accumulation did not abolish the ability of PGE2 to stimulate the DNA synthesis. The results do not support a role for adenylyl cyclase activation in the stimulatory effect of prostaglandins on hepatocyte growth. While the data are compatible with an involvement of phosphoinositide-specific phospholipase C in the growth-promoting effect of prostaglandins in cultured rat hepatocytes, they suggest this may not be the sole mechanism.