Oncology Association of Naturopathic Physicians: Principles of Care Guidelines.

Patient use of integrative oncology (the inclusion of nonconventional treatments alongside the conventional standard of care) continues to grow, with some studies showing its use in cancer patients to be as high as 91%. Naturopathic physicians are primary care providers who use integrative therapies to deliver patient-centred care. The Oncology Association of Naturopathic Physicians (oncanp) was formed in 2004 as a specialty association for naturopathic physicians providing integrative cancer care (nd oncs). Currently, the membership encompasses more than 400 naturopathic physicians and students, 115 of whom are board-certified Fellows of the American Board of Naturopathic Oncology. In 2016, oncanp established a committee comprising recognized experts in the field of naturopathic oncology to develop a Principles of Care (poc) guideline. The committee first undertook a review of existing standard-of-care and best-practice guidelines in the field of oncology and then adapted those concepts into a draft document. The draft document was then reviewed by naturopathic physicians, medical and radiation oncologists, naturopathic policy experts, and finally the oncanp membership at large. The poc document presented here provides clear guidelines for nd oncs on how best to deliver patient-centred care in the areas of assessment, treatment planning, care management, interprofessional collaboration, and survivorship care. This naturopathic oncology poc document can be a valuable resource for nd oncs and other oncology care providers to further an understanding of the naturopathic and integrative oncology care model and its potential for collaboration.

Missed opportunities for screening child contacts of smear-positive tuberculosis in Zambia, a high-prevalence setting.

OBJECTIVE: To evaluate whether contact screening recommendations for child household contacts of adult smear-positive tuberculosis (TB) cases were implemented in Lusaka, Zambia. METHODS: A cross-sectional survey of smear-positive adults receiving anti-tuberculosis treatment was conducted. The main outcomes were proportions of TB patients with under-five children who were aware, informed and/or had a child screened and/or commenced on isoniazid (INH). RESULTS: Of 371 TB patients (median age 33 years, 70% males), 259 (70%) lived with a child aged <15 years, of whom 48% (177) were aged <5 years. Overall, 32% (n = 119) were aware about child contact screening; 49% were informed by community agents vs. 38% by health care providers. Of the 259 TB patients with children, 32% (n = 84) were aware of contact screening, 32% (56/177) of whom had children aged <5 years. Of the 92/259 (36%) who were asked to have their children screened by the health care provider, 19% (49) complied. Of 177 eligible children, 11% (n = 20) were commenced on INH. Patients were more likely to comply when informed by the health care provider vs. the community agent. CONCLUSION: Screening of child contacts of adult smear-positive TB patients in areas with a large burden of adult disease is not routinely implemented. Interventions are required to ensure compliance with contact screening recommendations.

The incidence of congenital malformations and variations in Göttingen minipigs.

Knowledge of the incidence of spontaneous congenital abnormalities is critical for the accurate interpretation of findings in teratogenicity studies in any species. In this paper, results of the examination of 1739 neonatal Göttingen Minipigs are presented. Over the 2-year period under consideration, the incidence of external and visceral malformations was less than 0.2 and 0.1%, respectively. The most common external malformations were syndactyly, limb hyperflexion, domed head and scoliosis. The most common internal malformations were undescended testes, ventricular septal defect, diaphragmatic hernia and atrial septal defects. Pentadactyly and variation in the aortic arch's bifurcation (absent truncus bicaroticus) were the most common variations. These data will help support the use of the Göttingen Minipig as a non-rodent species in embryofetal development studies where concerns persist about the availability of background data.

Chemotactic clusters in confined run-and-tumble bacteria: a numerical investigation.

We present a simulation study of pattern formation in an ensemble of chemotactic run-and-tumble bacteria, focussing on the effect of spatial confinement, either within traps or inside a maze. These geometries are inspired by previous experiments probing pattern formation in chemotactic strains of E. coli under these conditions. Our main result is that a microscopic model of chemotactic run-and-tumble particles which themselves secrete a chemoattractant is able to reproduce the main experimental observations, namely the formation of bacterial aggregates within traps and in dead ends of a maze. Our simulations also demonstrate that stochasticity plays a key role and leads to a hysteretic response when the chemotactic sensitivity is varied. We compare the results of run-and-tumble particles with simulations performed with a simplified version of the model where the active particles are smooth swimmers which respond to chemotactic gradients by rotating towards the source of chemoattractant. This class of models leads again to aggregation, but with quantitative and qualitative differences in, for instance, the size and shape of clusters.

Filling an emulsion drop with motile bacteria.

We have measured the spatial distribution of motile Escherichia coli inside spherical water droplets emulsified in oil. At low cell concentrations, the cell density peaks at the water-oil interface; at increasing concentration, the bulk of each droplet fills up uniformly while the surface peak remains. Simulations and theory show that the bulk density results from a "traffic" of cells leaving the surface layer, increasingly due to cell-cell scattering as the surface coverage rises above ∼10%. Our findings show similarities with the physics of a rarefied gas in a spherical cavity with attractive walls.

Expression of alpha-fetoprotein and stem cell factor/c-kit system in bile duct ligated young rats.

The existence of a facultative hepatic stem cell compartment in bile ductules that participates in the renewal process of epithelial cell populations in the liver is well documented. The present study was undertaken to determine whether the immature bile epithelium responds differently to growth stimulus induced by bile stasis to that seen in the adult animal. In addition, the possible involvement of the growth factor/receptor systems associated with early activation of hepatic stem cells in bile duct proliferation was also examined. Bile duct ligation was used to induce the proliferation of bile epithelial cells. The expression of full-length alpha-fetoprotein (AFP) was used as an indicator for activation of the stem cell compartment. AFP was highly and selectively expressed in small bile ducts 7 days after bile duct ligation in immature rats up to 5 weeks of age. Although no significant increase in the expression of stem cell factor (SCF) c-kit, hepatocyte growth factor (HGF), and transforming growth factor-alpha (TGF-alpha) was observed 7 days after bile duct ligation in adult rats, the expression of all these growth factors was increased in bile duct ligated rats up to 5 weeks of age. These results suggest that the bile ductular epithelium in the young rats responds to bile stasis in a fashion that is phenotypically similar to that seen during early activation of hepatic stem cells in adult liver.

Precursor-product relationship between oval cells and hepatocytes: comparison between tritiated thymidine and bromodeoxyuridine as tracers.

The expansion and differentiation of oval cells in the acetylaminofluorene (AAF)/partial hepatectomy (PH) model was studied utilizing pulse-chase labeling with both tritiated thymidine ([3H]TdR) and bromodeoxyuridine (BUdR). Animals in which a significant decrease in serum albumin and increase in alanine aminotransferase and bilirubin were observed demonstrated the most prominent differentiation of oval cells into hepatocytes. Administration of [3H]TdR or BUdR, either individually or together, to the animals on day 6 after partial hepatectomy resulted in labeling of the majority of the oval cells by days 7 and 9 after PH. A striking difference in the distribution of [3H]TdR- and BUdR-labeled cells in the double labeling experiments was observed on day 11, at which time the number of [3H]TdR-labeled cells increased 6-fold and that of double labeled cells decreased 2-fold. Furthermore, on day 11 the basophilic foci were weakly positive for BUdR and negative at later time points in animals receiving BUdR alone or together with [3H]TdR. In contrast, the cells in basophilic foci as well as transitional cells were positive for [3H]TdR. Cells heavily labeled with both [3H]TdR and BUdR were present at all time points, indicating an inhibition of the proliferative activity. Pulse labeling of rat liver epithelial cells with BUdR in vitro demonstrated that immunodetection of BUdR was lost after three or more cell divisions. We conclude that the BUdR tagging method is particularly sensitive to label dilution during cell cycling and may not be suitable for establishment of a precursor-product relationship between cell lineages when the progenitor population proliferates more than three times.

Social support and its relationship to immunization status in preschool children.

Many children are at risk for developing serious and costly health problems because they are not adequately immunized. This descriptive correlational study explored the relationship between social support, parental knowledge of vaccine-preventable diseases, and the immunization status of preschool children. A convenience sample of 153 parents and guardians of children aged 6 to 24 months completed Procidano and Heller's Perceived Social Support Scales, a questionnaire on immunization knowledge, and a demographics questionnaire. Data indicating completeness of immunizations were obtained from the children's health records. Point-biserial statistical analysis revealed a positive relationship between immunization status and social support (r = .29; p = .0003). This finding supports those of past studies that identified a positive relationship between social support and preventive health practices. No relationship was found between immunization status and parental knowledge of vaccine-preventable diseases. Assessment of social support can assist nurses in identifying children at risk for incomplete immunizations and in isolating potential reasons for the deficiency.

Expression of leukemia inhibitory factor and its receptor during liver regeneration in the adult rat.

Leukemia inhibitory factor (LIF) is a polyfunctional cytokine that was discovered in the conditioned medium from Buffalo rat liver cells. In the liver, LIF is known to induce acute phase proteins in the hepatocytes. No comprehensive study has yet been performed on the physiological role of this cytokine during liver regeneration. Thus, we studied the level of expression and cellular distribution of transcripts for LIF, its receptor (LIFR), and signal transducing subunit gp13O during rat liver regeneration after both simple partial hepatectomy (PH) and the oval cell activation induced by the combination of 2-acetylaminofluorene and PH. In addition, the expression of an acute phase protein alpha1-acidglycoprotein was examined. The level of transcripts for LIF and its receptor subunits increased and remained elevated during oval cell expansion. In contrast, after PH, the transcripts were induced only transiently, showing a peak 24 hours after the operation. LIF and receptor subunits were expressed in both parenchymal and nonparenchymal fractions in the 2-acetylaminofluorene/PH model, but the level of expression was most pronounced in the nonparenchymal fraction. In situ hybridization clearly revealed a strong expression of LIF, LIFR, and gp13O in the oval cells and demonstrated only a weak expression in the parenchyma. Interestingly, transcripts of alpha1-acidglycoprotein were exclusively detected in the parenchyma. These results suggest a phenotypic difference between oval cells and hepatocytes in their signaling through gp130. We hypothesize that the LIF/LIFR gp130 system may be involved in the expansion and differentiation of the liver stem cell compartment.

Coexpression of stem cell factor and c-kit in embryonic and adult liver.

Stem cell factor and its receptor c-kit constitute an important signal transduction system implicated in survival, proliferation, and differentiation of stem cells in hematopoiesis, gametogenesis, and melanogenesis. In the present study we used both immunocytochemical methods and Western analysis to demonstrate the presence of this cytokine/receptor system in both embryonic and adult rat liver. Stem cell factor was present in the ductular cells around the portal vein during the late embryonic stage of the liver. In the adult liver both bile ducts and bile ductules were positive for stem cell factor and c-kit. When the activation of the liver stem cell compartment was induced by combining administration of acetylaminofluorene and partial hepatectomy, both stem cell factor and c-kit were expressed in the infiltrating oval cell population, but absent in the newly formed basophilic hepatocytes. Activation of oval cell proliferation following administration Of D-galactosamine also produced a similar but less prominent increase in the level of the stem cell factor. Our data suggest that the stem cell factor/c-kit signal transduction system is involved in the development of bile ducts and that it may also be an important member of the growth factor/receptor systems associated with the biology of liver stem cells.

Expression of transforming growth factor alpha/epidermal growth factor receptor, hepatocyte growth factor/c-met and acidic fibroblast growth factor/fibroblast growth factor receptors during hepatocarcinogenesis.

It is widely believed that abnormal production of polypeptide growth factors, together with other molecular alterations, play an important role in neoplastic development. Transforming growth factor alpha (TGFalpha), hepatocyte growth factor (HGF) and acidic fibroblast growth factor (aFGF) are the three major growth factors that contribute to liver regeneration occurring via both hepatocyte replication and oval cell proliferation. It is not clear, however, whether and to what extent these growth factors are also involved in hepatocarcinogenesis. In the present study, the gene expression of TGFalpha, HGF and aFGF and their corresponding receptors was examined by Northern blotting and in situ hybridization during hepatocarcinogenesis induced by the Solt-Farber protocol. All three growth factor/receptor systems, TGFalpha/epidermal growth factor receptor (EGFR), HGF/c-met and aFGF/FGF receptors (flg and bek) were significantly elevated at early time points when oval cells were proliferating. Their respective expression decreased after 1 month and remained at a low level until the development of liver tumors. In all hepatocellular carcinomas (HCC) examined, the transcripts of TGFalpha and aFGF were highly expressed, while those of HGF were low. With regard to the receptor expression in the tumors, EGFR was present at varying levels, c-met was expressed at higher levels and flg increased significantly, whereas bek remained at low levels. These data suggest that TGFalpha and aFGF are the major growth factors involved in the progression of HCC, and that the signal of aFGF is mainly transduced by the receptor flg in HCC. Furthermore, HCC cells were phenotypically very similar to oval cells with regard to the gene expression of growth factor/receptor systems. These results, along with the finding that all the HCC cells are positive for the oval cell antigen OV6, and that cytokeratin 19 is heavily expressed in both tumor and oval cells, strongly suggest that at least some of the HCC induced by the Solt-Farber protocol may be derived from oval cells.

Effect of vitamin A deficiency on the integrity of hepatocytes after partial hepatectomy.

The effect of vitamin A deficiency on hepatic regeneration in male and female rats was studied after partial hepatectomy. A fourfold increase in the number of positive dUTP end-labeled nuclei was observed in the deficient animals as early as 30 minutes after partial hepatectomy and their number reached a peak by 8 hours after the operation. The bile duct cells were both morphologically and biochemically intact at all time points. Administration of retinyl palmitate 1 hour before partial hepatectomy significantly reduced the number of positive nuclei, and treatment with retinyl palmitate 24 or 48 hours before the operation reduced the number of positive cells to the level observed in control vitamin A-supplemented rats. The level of transcripts for c-jun, c-fos, c-myc, and transforming growth factor-beta 1 were increased for an extended period of time in livers of deficient animals, whereas the expression of both p53 and max were unchanged. Immunocytochemistry demonstrated the presence of latent transforming growth factor-beta 1 in cells showing evident apoptotic or necrotic changes in their nuclei. This study demonstrates the importance of vitamin A for the survival of hepatocytes both in intact vitamin A-deficient liver and after partial hepatectomy, whereas the ductal cells appear to be less sensitive to vitamin A deficiency.

Expression of fibroblast growth factor receptors flg and bek during hepatic ontogenesis and regeneration in the rat.

Fibroblast growth factors (FGFs) mediate their cellular responses through specific cell surface receptors. Previous studies have indicated that acidic FGF is involved in liver regeneration and hepatic differentiation via the stem cell compartment, as well as in liver development (Marsden et al., Lab. Invest. 67:427-433, 1992). To further define the role of acidic FGF and its receptor systems in the liver, we examined the expression and cellular localization of FGF receptor-1 (flg) and FGF receptor-2 (bek) in the liver by Northern blot analysis and in situ hybridization techniques during liver regeneration, hepatic differentiation, and ontogenesis. In the normal adult liver, flg is absent in hepatocytes, whereas a low level of bek can be detected. The transcripts for bek increased, while flg exhibited little change during liver regeneration after partial hepatectomy. Both flg and bek were expressed at high levels in the developing liver. flg was expressed at a high level in embryonic liver and further increased after birth, whereas a significant increase of bek occurred at the postnatal stage of liver development. In the 2-acetylaminofluorene/partial hepatectomy model, both flg and bek are expressed at high levels during the period of active proliferation and differentiation of oval cells. In situ hybridization showed that flg was mainly localized in oval cells, whereas bek was highly expressed in both oval and Ito cells. The data suggest that bek is involved in the proliferation of mature hepatocyte proliferation during liver regeneration, while flg is characteristic of primitive hepatic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic regeneration in vitamin A-deficient rats: changes in the expression of transforming growth factor alpha/epidermal growth factor receptor and retinoic acid receptors alpha and beta.

We have studied the effect of vitamin A deficiency on the expression of transforming growth factor alpha (TGF-alpha), hepatocyte growth factor, acidic fibroblast growth factor, and TGF-beta 1 after partial hepatectomy of vitamin A-supplemented and vitamin A-deficient rats. In addition, the expressions of epidermal growth factor receptor and retinoic acid receptors alpha (RAR alpha) and beta (RAR beta) were studied. Partial hepatectomy was performed on the animals from the vitamin A-supplemented and -deficient groups at the age of 10 weeks when the weights of the animals on the deficient diet had reached a plateau. Two animals from each group were sacrificed before the operation and also 12, 24, 48, and 72 h and 5 days after the operation. Partial hepatectomy of the vitamin A-deficient rats leads to a focal necrosis of liver followed by a rapid restoration of liver mass. Expression of the TGF-alpha and epidermal growth factor receptor was highly elevated in the livers of deficient animals after partial hepatectomy. In the vitamin A-supplemented animals, the level of epidermal growth factor receptor was down-regulated following partial hepatectomy. Proliferation of oval cells in vitamin A-deficient livers following partial hepatectomy and subsequent increase in 2.1-kilobase alpha-fetoprotein mRNA was observed, suggesting an activation of the stem cell compartment. Another unexpected result was an inverse relationship between RAR beta and RAR alpha expression, the latter becoming the major species after partial hepatectomy in animals on the vitamin A-deficient regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of stem cell factor and its receptor, c-kit, during liver regeneration from putative stem cells in adult rat.

BACKGROUND: Stem cell factor (SCF) and its receptor, c-kit, are known to play important roles in hematopoiesis, melanogenesis, and gametogenesis. The biologic effects of the SCF/c-kit system are believed to involve survival, proliferation, and migration of early stem cell progeny. Although SCF and c-kit receptor are widely expressed during normal embryonic development, their expression in the adult is limited. EXPERIMENTAL DESIGN: The expression of SCF and c-kit genes was examined during liver regeneration via the oval cell compartment utilizing partial hepatectomy (PH) combined with the administration of a noncarcinogenic dose of 2-acetylaminofluorene (AAF) for 8 days (AAF/PH model). RESULTS: Both the ligand and the receptor genes were expressed during the early stages of oval cell proliferation after partial hepatectomy in the AAF/PH model, while neither simple partial hepatectomy nor AAF administration alone induced a noticeable expression of the SCF/c-kit system. The level of SCF mRNA increased within 12 hours after partial hepatectomy and reached a peak around day 4. Thus, the expression of SCF preceded the major expansion of the oval cell compartment. The level of c-kit transcripts gradually increased from the 12-hour time point and stayed elevated until day 11, when a large proportion of the oval cells differentiated into small basophilic hepatocytes. Separation of liver cells at day 3 in the AAF/PH model into parenchymal and nonparenchymal fractions demonstrated that the expression of both SCF and c-kit receptor genes was restricted to the nonparenchymal cells. Furthermore, in situ hybridization revealed that the c-kit transcripts were restricted to oval cells, whereas the SCF transcripts were expressed in both oval cells and Ito cells. CONCLUSIONS: The transcripts for the c-kit receptor are expressed in the early progeny of the hepatic stem cells. The SCF/c-kit system may, possibly in combination with other growth factor/receptor systems, be involved in the early activation of the hepatic stem cells as well as in the expansion and differentiation of oval cells.

Activation of hepatic stem cell compartment in the rat: role of transforming growth factor alpha, hepatocyte growth factor, and acidic fibroblast growth factor in early proliferation.

We have demonstrated previously a pronounced increase in the expression of hepatocyte growth factor (HGF) (Z. Hu, R. P. Evarts, K. Fujio, E. R. Marsden, and S. S. Thorgeirsson, Am. J. Pathol., 142: 1823-1830, 1993), transforming growth factor alpha (TGF-alpha) (R. P. Evarts, H. Nakatsukasa, E. R. Marsden, Z. Hu, and S. S. Thorgeirsson, Mol. Carcinog., 5: 25-31, 1992), and acidic fibroblast growth factor (aFGF) (E. R. Marsden, Z. Hu, K. Fujio, H. Nakatsukasa, S. S. Thorgeirsson, and R. P. Evarts, Lab. Invest., 67: 427-433, 1992) that coincided with the proliferation and differentiation of putative hepatic stem cells and perisinusoidal stellate (Ito) cells. Here, we examine the earliest stages of stem cell activation in rat liver using an experimental model involving treatment with acetylaminofluorene and partial hepatectomy (R. P. Evarts, P. Nagy, E. Marsden, and S. S. Thorgeirsson, Carcinogenesis (Lond.), 8: 1737-1740, 1987). Histochemical identification of stem cell progeny and Ito cells was accomplished by OV6 and desmin antibodies, respectively. Expression of the 2.1-kilobase alpha-fetoprotein transcripts and the concomitant DNA synthesis ([3H]thymidine label) were used as indicators for the activation of the stem cell compartment. Expression of HGF, TGF-alpha, and aFGF was analyzed at the time of partial hepatectomy and 4, 12, 24, 48, 72, and 92 h after the operation. [3H]-Thymidine-labeled OV6- and desmin-positive cells were present in the portal space and in the Glisson capsule 4 h after partial hepatectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of hepatocyte growth factor and c-met genes during hepatic differentiation and liver development in the rat.

Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes in vitro. The receptor for HGF has recently been characterized as the product of the proto-oncogene c-met. We have examined the possible involvement of HGF in hepatic growth and differentiation in the rat. The experimental systems used were acetylaminofluorene treatment combined with partial hepatectomy to induce proliferation and differentiation of oval cells in adult liver and the pre- and postnatal liver. In the acetylaminofluorene model, Northern blot analysis showed that level of HGF transcripts increased one day after partial hepatectomy, reached a peak by day 6, were maintained at that level until day 13, and then declined, reaching normal level at 20 days. The expression of c-met also increased gradually, reached a peak around 9 to 13 days after partial hepatectomy, at which time oval cell proliferation was most prominent. In the developing liver, an elevated level of HGF transcripts was found between 4 and 21 days after birth. The expression of c-met also slightly increased at the same time. In situ hybridization showed that the transcripts for HGF were localized in desmin-positive Ito cells, whereas the transcripts for c-met were strongly expressed by oval cells. We have shown earlier that Ito cells and oval cells proliferate simultaneously and exist in close proximity in the acetylaminofluorene model and that Ito cells are a primary source of growth factors such as transforming growth factor-alpha and acidic fibroblast growth factors. The data presented here suggest that HGF is, in combination with other growth factors, involved in the proliferation and differentiation of oval cells via a paracrine mechanism.

Occurrence of oval-type cells in hepatitis B virus-associated human hepatocarcinogenesis.

Proliferation of a new population of epithelial cells with distinct structure, as well as cytokeratin and alpha-fetoprotein expression, was observed in nonneoplastic liver tissues from 14 cases (13 hepatitis B virus-positive) of human hepatocellular carcinoma. These cells were characterized by oval nuclei; scant, pale cytoplasm; small cell size; and cross-reaction with a monoclonal antibody against rat oval cells. These putative human oval cells were strongly positive for cytokeratin 19 and displayed considerable heterogeneity in alpha-fetoprotein and albumin expression. The oval cells were most prominent in actively regenerating nodules and in liver tissue surrounding the cancer. Oval cells and transitional types of cells appear to be the principal producers of alpha-fetoprotein in the regenerating liver. Cancer cells positive for cytokeratins 8, 18 and 19 were observed in half the hepatocellular carcinomas studied. The data suggest that a new cell population structurally similar to oval cells seen in early stages of chemical hepatocarcinogenesis in rats is consistently present in regenerating liver lesions associated with human hepatocellular carcinoma. Furthermore, it is possible that the proliferation of these oval-type cells may partly account for the elevation of serum alpha-fetoprotein frequently seen in precancerous stages of hepatitis B virus-associated human hepatocellular carcinoma.

Expression of acidic fibroblast growth factor in regenerating liver and during hepatic differentiation.

BACKGROUND: Acidic fibroblast growth factor belongs to a family of growth factors that show a high affinity for heparin sulfate proteoglycans. In vitro, it participates in various cellular functions including proliferation, differentiation, angiogenesis, and cell migration, but in vivo, the physiologic role of this growth factor is still not clearly defined. EXPERIMENTAL DESIGN: The level of expression and also cellular distribution of transcripts for acidic fibroblast growth factor (aFGF) were studied in adult rat liver after partial hepatectomy and during hepatic differentiation in fetal, neonatal, and adult livers by Northern analysis and in situ hybridization techniques. RESULTS: After partial hepatectomy a significant increase in the transcripts for aFGF was observed at 24 hours, whereas at 4 and 12 hours after the operation, the level of transcripts were similar to those of sham-operated animals. In the postnatal liver a high level of aFGF expression was present when the most evident transition from 2 to 3 cell thick hepatic cords to normal hepatic structure is taking place (Ogawa K, Medine A, Farber E. Br J Cancer 1979;40: 782-90). In contrast during the prenatal period, when the liver is still a hemopoietic organ and only a small number of sinusoids are present, low level of aFGF transcripts could be found. Animals treated with 2-acetylaminofluorene and partial hepatectomy (Evarts RP, Nagy P, Marsden E, Thorgeirsson SS. Carcinogenesis 1987;8:1737-40) displayed a marked increase in hepatic aFGF transcripts at the peak of proliferation of primitive liver epithelial cells (oval cells) and perisinusoidal stellate cells (Ito cells) in addition to hepatocytes. In situ hybridization combined with immunocytochemistry using oval and Ito cell specific antibodies revealed the presence of transcripts both in oval cells and Ito cells. Basophilic areas composed of small hepatocytes had a 3-fold increase in the level of transcripts as compared with the surrounding hepatocytes. CONCLUSIONS: These experiments demonstrate that the expression of aFGF is highest during the late stages of hepatic morphogenesis in newborn animals as well as during hepatic differentiation in adult liver.