Biomedical subjects

J Farris

Publications and source records attributed to J Farris.

17 recordsLinked to original sources

PubMed2006

Evaluation of aquatic toxicities of chromium and chromium-containing effluents in reference to chromium electroplating industries.

This study evaluated aquatic toxicities of chromium and chromium-containing laboratory samples representative of effluents from chromium electroplating industries, and compared the aquatic environmental risks of hexavalent and trivalent chromium electroplating operations. Trivalent chromium electroplating has emerged as an acceptable alternative to hazardous hexavalent chromium electroplating. This process substitution has reduced the human health impact in the workplace and minimized the production of hazardous sludge regulated under the Resource Conservation and Recovery Act (RCRA). The thrust behind this research was to investigate whether trivalent chromium electroplating operations have lower adverse impacts on standardized toxicity test organisms. Ceriodaphnia dubia and Pimephales promelas were used to investigate toxicities of trivalent chromium (Cr (III)), hexavalent chromium (Cr (VI)), and industrial effluents. In agreement with previous studies, Cr (III) was found to be less toxic than Cr (VI). Despite having several organic and inorganic constituents in the effluents obtained from trivalent chromium plating baths, they exhibited less adverse effects to C. dubia than effluents obtained from hexavalent chromium electroplating baths. Thus, transition from hexavalent to trivalent chromium electroplating processes may be justified. However, because of the presence of organic constituents such as formate, oxalate, and triethylene glycol in effluents, trivalent chromium electroplating operations may face additional regulatory requirements for removal of total organic carbon.

Animals↗

PubMed2001

The rapid destabilization of p53 mRNA in immortal chicken embryo fibroblast cells.

The steady-state levels of p53 mRNA were dramatically lower in immortal chicken embryo fibroblast (CEF) cell lines compared to primary CEF cells. In the presence of cycloheximide (CHX), the steady-state levels of p53 mRNA markedly increased in immortal CEF cell lines, similar to levels found in primary cells. The de novo synthetic rates of p53 mRNA were relatively similar in primary and immortal cells grown in the presence or absence of CHX. Destabilization of p53 mRNA was observed in the nuclei of immortal, but not primary, CEF cells. The half-life of p53 mRNA in primary cells was found to be a relatively long 23 h compared to only 3 h in immortal cells. The expression of transfected p53 cDNA was inhibited in immortal cells, but restored upon CHX treatment. The 5'-region of the p53 mRNA was shown to be involved in the rapid p53 mRNA destabilization in immortal cells by expression analysis of 5'- and 3'-deleted p53 cDNAs as well as fusion mRNA constructs of N-terminal p53 and N-terminal deleted LacZ genes. Together, it is suggestive that the downregulation of p53 mRNA in immortal CEF cells occurs through a post-transcriptional destabilizing mechanism.

Animals↗

PubMed2001

Necrotic cell death by hydrogen peroxide in immortal DF-1 chicken embryo fibroblast cells expressing deregulated MnSOD and catalase.

The reactive oxygen species are known as endogenous toxic oxidant damaging factors in a variety of cell types, and in response, the antioxidant genes have been implicated in cell proliferation, senescence, immortalization, and tumorigenesis. The expression of manganese superoxide dismutase mRNA was shown to increase in most of the immortal chicken embryo fibroblast (CEF) cells tested, while expression of catalase mRNA appeared to be dramatically decreased in all immortal CEF cells compared to their primary counterparts. The expression of copper-zinc superoxide dismutase mRNA was shown to increase slightly in some immortal CEF cells. The glutathione peroxidase expressed relatively similar levels in both primary and immortal CEF cells. As primary and immortal DF-1 CEF cells were treated with 10-100 microM of hydrogen peroxide (concentrations known to be sublethal in human diploid fibroblasts), immortal DF-1 CEF cells were shown to be more sensitive to hydrogen peroxide, and total cell numbers were dramatically reduced when compared with primary cell counterparts. This increased sensitivity to hydrogen peroxide in immortal DF-1 cells occurred without evident changes in either antioxidant gene expression, mitochondrial membrane potential, cell cycle distribution or chromatin condensation. However, the total number of dead cells without chromatin condensation was dramatically elevated in immortal DF-1 CEFs treated with hydrogen peroxide, indicating that the inhibition of immortal DF-1 cell growth by low concentrations of hydrogen peroxide is due to increased necrotic cell death, but not apoptosis. Taken together, our observation suggests that the balanced antioxidant function might be important for cell proliferation in response to toxic oxidative damage by hydrogen peroxide.

Animals↗

PubMed2001

Post-transcriptional inactivation of p53 in immortalized murine embryo fibroblast cells.

The steady-state levels of p53 mRNA and protein were barely detectable by Northern and Western blot analysis in spontaneously immortalized (10)3 and (10)7 murine embryo fibroblast (MEF) cells. But when cells were treated with cycloheximide (CHX) or emetine, expression levels were restored to those observed in primary and immortal (10)10 MEF cells. However, levels of p53 mRNA were not changed in primary or (10)10 MEF cells by CHX treatment. De novo p53 mRNA synthetic rates were similar in primary, (10)10, (10)3, and (10)7 MEF cells treated with or without CHX. Treatment with actinomycin D (ActD) showed that p53 mRNA in primary and (10)10 MEF cells had a relatively long half-life of 22 h, compared to less than 2 h for (10)3 and (10)7 MEF cells. Pulse-chase analysis of p53 mRNA turnover using CHX and ActD showed that the rapid destabilization of p53 mRNA in (10)3 and (10)7 MEF cells could be regulated at the transcriptional and translational levels. In addition, the destabilization of p53 mRNA appeared to occur in the nucleus for (10)3 and (10)7 cells, but not for primary and (10)10 MEF cells. Taken together, the present study demonstrates that inactivation of the p53 gene occurs at the post-transcriptional level by rapid destabilization of its mRNA in the nucleus of spontaneously immortalized (10)3 and (10)7 MEF cells.

Animals↗

PubMed2001

Alterations in p53 and E2F-1 function common to immortalized chicken embryo fibroblasts.

A number of non-virally and non-chemically immortalized chicken embryo fibroblast (CEF) cells have been established recently in continuous cell culture. All immortal CEF cells tested showed common genetic alterations in the expression patterns of p53 and E2F-1 mRNA and protein which were down- and up-regulated, respectively. The biological effects of differentially regulated p53 and E2F-1 were determined by reporter gene transcriptional activity assays, DNA binding assays, and Northern blot analysis of the expression patterns of down-stream genes. In addition, expression of most of the cyclin genes was up-regulated in immortal CEF cells, which may be associated with the rapid cell division rates and serum-independent growth patterns seen in immortal CEF cells. The telomeric lengths and chromosome integrity were maintained in all immortal CEF cell lines without detectable telomerase activity. Although the functional inactivations of the p53 and Rb regulatory pathways are known to be common events for cellular immortalization, the genetic changes leading to alteration of p53 and E2F-1 function through transcriptional and post-transcriptional regulation seem to be unique in immortal CEF cells.

Carrier Proteins↗

PubMed2001

Increased mitochondrial-encoded gene transcription in immortal DF-1 cells.

We have established, in continuous cell culture, a spontaneously immortalized chicken embryo fibroblast (CEF) cell line (DF-1) as well as several other immortal CEF cell lines. The immortal DF-1 cells divided more rapidly than primary and other immortal CEF cells. To identify the genes involved in rapidly dividing DF-1 cells, we have used differential display RT-PCR. Of the numerous genes analyzed, three mitochondrial-encoded genes (ATPase 8/6, 16S rRNA, and cytochrome b) were shown to express at higher levels in DF-1 cells compared to primary and other immortal CEF cells. The inhibition of mitochondrial translation by treatment with chloramphenicol markedly decreased ATP production and cell proliferation in DF-1 cells, while not affecting growth in either primary or other immortal CEF cells. This result suggests a correlation between rapid cell proliferation and the increased mitochondrial respiratory functions. We also determined that the increased transcription of mitochondrial-encoded genes in DF-1 cells is due to increased de novo transcript synthesis as shown by mitochondrial run-on assays, and not the result of either increased mitochondrial biogenesis or mitochondrial transcript half-lives. Together, the present studies suggest that the transcriptional activation of mitochondrial-encoded genes and the elevated respiratory function should be one of the characteristics of rapidly dividing immortal cells.

Adenosine Triphosphate↗

PubMed2001

Differential expression of chicken dimerization cofactor of hepatocyte nuclear factor-1 (DcoH) and its novel counterpart, DcoHalpha.

We have used differential display PCR to study altered gene expression in immortalized chicken embryo fibroblasts (CEFs) that have been established in our laboratory. This technique resulted in the cloning of a novel counterpart of the previously cloned chicken dimerization cofactor of hepatocyte nuclear factor (HNF)-1 (cDcoH), which was identified as cDcoHalpha. The steady-state mRNA levels of cDcoHalpha were up-regulated in all immortal CEFs tested compared with primary CEF cells. cDcoH and cDcoHalpha showed opposite patterns of mRNA expression due to differential regulation of transcription rates, but not mRNA half-lives, in primary and immortal CEFs. Expression of cDcoHalpha increased in the late G1 and early S phases of the cell cycle, while cDcoH mRNA increased in the late S and G2/M phases. In contrast with consistent expression of both genes in primary quiescent cells, cDcoH mRNA, but not cDcoHalpha mRNA, was dramatically decreased in primary senescent cells. The highest levels of cDcoHalpha mRNA were found in the kidney, liver, heart and ovarian follicles, while the major tissues expressing cDcoH were hypothalamus, kidney and liver. cDcoH and cDcoHalpha probes did not cross-hybridize to human hepatocyte mRNA. When transfected into human HepG2 cells, both cDcoH and cDcoHalpha showed similar functional activity as measured by increased expression of a reporter gene, as well as alpha-fetoprotein and albumin genes that both contain HNF-1 binding elements in their promoters. Our results suggest that the novel chicken DcoHalpha might function as a transcriptional cofactor for HNF-1 in specific cellular-environmental states.

Age Factors↗

PubMed2001

Molecular cloning and expression analysis of the turkey vasoactive intestinal peptide receptor.

Vasoactive intestinal peptide (VIP) is a prolactin (PRL)-releasing factor whose activity in avian species is believed to be mediated by a specific VIP receptor (VIP-R). Circulating PRL levels are closely related to hypothalamic VIP immunoreactivity, hypothalamic VIP mRNA content, and hypophysial-portal blood VIP concentrations in turkeys. In the present study, a turkey VIP-R (tVIP-R) cDNA was cloned and its mRNA abundance was quantified in various tissues during different reproductive stages. The 2347-bp tVIP-R cDNA encoded a 457 amino acid protein, with a predicted Mr of 52 kDa. The full-length cDNA shares approximately 55% similarity with the mammalian VIP receptor-1. Northern blot analysis revealed that a major 2.7-kb transcript was expressed in laying hen pituitaries. Furthermore, two minor tVIP-R transcripts of 3.7 and 3.4 kb were observed. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was performed using RNA from various turkey brain and peripheral tissues throughout the reproductive cycle. The steady-state levels of pituitary tVIP-R mRNA changed during the reproductive cycle, whereas mRNA expression in other tissues was not affected. The steady-state levels of tVIP-R mRNA were only affected in the pituitary, whereas mRNA expression in any of the other tissues examined following the immunization of turkeys against VIP were not affected.

Amino Acid Sequence↗

PubMed2001

Gonad-specific expression of two novel chicken complementary DNA isoforms.

Differential display reverse transcription polymerase chain reaction was used to isolate a novel cDNA clone (C47) that was initially shown to be downregulated in senescent chicken embryo fibroblast cells. In a tissue environment, C47 transcripts were only detected in gonadal tissue. The expression of the larger isoform (C47L) was essentially restricted to the ovary, and the smaller isoform (C47S) was predominately expressed in the testis. Although levels of the C47L mRNA were relatively high in both the small white and the developing larger follicles, there was very low expression in regressed and postovulated follicles. Nucleotide sequence analysis indicated that two different transcripts of the single-copy C47 gene were generated by differential polyadenylation in the 3' untranslated region. As a result of a single nucleotide deletion, the C47L mRNA produced a smaller 48-kDa protein, and the C47S mRNA generated a larger 57-kDa protein when both were translated in vitro. Both protein isoforms were shown to contain conserved C2H2 Zn finger motifs and nuclear localization signals suggestive of being putative transcription factors. These results suggest that the C47L and C47S isoforms might play an important role in the regulation and maintenance of ovarian and testicular functions, respectively, in the chicken.

Amino Acid Sequence↗

PubMed2000

Molecular cloning and characterization of alternatively spliced transcripts of the turkey pituitary adenylate cyclase-activating polypeptide.

Pituitary adenylate cyclase-activating polypeptide (PACAP) increases the release of growth hormone (GH) and prolactin (PRL) in mammals. However, the evolutionary and functional relationships of PACAP, GH, and PRL are not clear. To understand how PACAP is regulated in the turkey, a turkey PACAP (tPACAP) cDNA has been cloned by the combination of reverse transcription-polymerase chain reaction and the rapid amplification of cDNA 5'- and 3'-ends. The deduced amino acid sequence of tPACAP-38 and turkey PACAP-related peptide (tPRP) displayed 87-97 and 52-63% similarity when compared to a variety of known PACAP-38 and PRP sequences, respectively. Two major transcripts (1.3 and 3.0 kb) of tPACAP were detected by Northern blot analysis. The highest levels of tPACAP mRNA were shown to be expressed in the hypothalamus, the cerebellum, and the cerebrum. In contrast, most of the other tissues tested expressed relatively low steady-state levels of tPACAP mRNA. Alternative splicing of tPACAP resulted in the expression of two different isoforms. The smaller form of tPACAP was expressed in the hypothalamus during early embryonic development and decreased significantly in later stages.

Alternative Splicing↗

PubMed2000

Creatine supplementation patterns and perceived effects in select division I collegiate athletes.

OBJECTIVE: To describe patterns of creatine use in select Division I collegiate athletes based on recommended dosages according to body weight. Further, to report the perceived effects noted with creatine supplementation. DESIGN: Anonymous open-ended self-report descriptive questionnaire. SETTING: National Collegiate Athletic Association Division I institution. PARTICIPANTS: Two-hundred and nineteen male and female collegiate athletes representing eight varsity sports. MAIN OUTCOME MEASURE(S): An open-ended questionnaire was administered to determine patterns of creatine use during the loading and maintenance phases of this nutritional supplement. In addition, perceived positive, negative, and no effects associated with creatine usage patterns were determined from athlete responses on this self-report measure. RESULTS: Considering this select group of collegiate athletes, highly variable patterns of creatine supplementation were noted for loading/maintenance phases based on recommended dosages/days and body weight. Of the 219 athletes surveyed, 90 (41%) reported using creatine, while creatine supplementation was more prevalent among men than women. Creatine users (80 athletes, 89%) reporting perceived positive effects were primarily at or below recommended dosages for the loading phase but above recommended dosages in the maintenance phase. Creatine users (34 athletes, 38%) reporting perceived negative effects were primarily at or below recommended dosages in the loading phase but noticeably above recommended dosages in the maintenance phase. Ironically, all creatine users who reported negative side effects also reported positive effects. Creatine users (10 athletes, 11%) reporting no effects were below recommended loading dosages but above recommended maintenance dosages. CONCLUSIONS: The perceived positive effects noted support current research (strength/weight gains), while the perceived negative effects (cramping/gastrointestinal distress) were consistent with anecdotal reports surrounding creatine supplementation. Apparently, collegiate athletes in this study are in need of education regarding the proper use of creatine supplementation. Additional studies are needed to ascertain creatine supplementation patterns of collegiate athletes in various settings.

Adolescent↗

PubMed1996

Factors associated with finishing status for dogs competing in a long-distance sled race.

OBJECTIVE: To determine whether selected factors were associated with finishing status in a long-distance sled dog race. DESIGN: Prospective, observational study. ANIMALS: 248 dogs participating in the 1994 Iditarod trail sled race that were members of 13 teams that finished the race. Dogs were not selected randomly, but were members of teams that were easily accessible for examination before the race. The proportion of teams that were examined that finished the race (14/17) was similar to the proportion of teams that were not examined that finished the race (36/41). PROCEDURE: Age, sex, body conformation (weight, length, and thoracic width and circumference), cardiac variables (heart rate, natural logarithm of heart period variance, PR interval, QRS duration, QT index, R wave amplitude in leads II and V3, mean electrical axis, presence of cardiac arrhythmias suggestive of myocardial disease), and athletic ranking as assessed by the musher were compared between dogs that finished the race (n = 128) and dogs that did not finish (n = 120). RESULTS: The only factor found to differ significantly (P < 0.05) between finishers and nonfinishers was athletic ranking as assessed by the musher. Athletic rank and QRS duration or QRS duration normalized for body weight were identified by means of logistic regression as variables associated (P < 0.15) with finishing status. There was a significant (P < 0.0001), but weak (R2 = 0.18), linear relationship between race time and mean QRS duration for each team. CLINICAL IMPLICATIONS: Athletic ranking as assessed by the musher was the most important of the studied variables in determining finishing status, whereas age, sex, body conformation, and body weight were unimportant. Duration of the QRS was of minor importance in determining finishing status.

Animals↗

PubMed1995

Tissue-specific alternative splicing of turkey preprovasoactive intestinal peptide messenger ribonucleic acid, its regulation, and correlation with prolactin secretion.

Although vasoactive intestinal peptide (VIP) is a well characterized physiological PRL-releasing factor in avian species, its regulated expression is not fully understood. We cloned complementary DNAs encoding the prepro-turkey VIP (prepro-tVIP) molecule from an adult turkey hypothalamic complementary DNA library. When the amino acid sequence of the prepro-tVIP was compared to chicken and mammalian sequence, it was found that the isolated tVIP molecules lacked the 27-amino acid peptide histidine isoleucine (PHI) portion of the precursor protein. Several tissues showed an alternatively spliced tVIP transcript that lacked the PHI sequence. Only in the hypothalamus did tVIP-specific primer pairs and reverse transcription-polymerase chain reaction produce two alternatively spliced fragments. The larger hypothalamus-specific fragment was subjected to nucleotide sequence analysis and identified as containing the alternatively spliced PHI-containing exon, which encoded a 27-amino acid PHI peptide in addition to the 8 amino acids that flanked the peptide. Hypothalamic tVIP expression was shown to be up-regulated during the incubation phase of the reproductive cycle. The increased steady state level of tVIP messenger RNA appears to be regulated by nesting behavior, because nest deprivation dramatically suppressed its expression. Levels of the minor tVIP transcript containing both the PHI- and VIP-encoding exons did not significantly change between reproductive stages and were maintained at approximately 4-6% of the total tVIP transcript level. Our findings provide further evidence that VIP is the most important PRL-releasing factor in birds. Our study should serve as a useful model for determining whether PHI contributes in any way to the physiological role of PRL regulation. Revealing the tissue distribution of VIP and PHI gene expression and tissue-specific alternative splicing could contribute to an understanding of the physiological functions of the two peptides as well as their relative roles in PRL regulation.

Alternative Splicing↗

PubMed1992

Basic fibroblast growth factor in cells derived from Dupuytren's contracture: synthesis, presence, and implications for treatment of the disease.

Dupuytren's contracture (DC) is associated with fibroblast and endothelial cell proliferation. We have identified a fibroblast and endothelial cell mitogen, basic fibroblast growth factor (FGF), in cells derived from this tissue and characterized the effects of this growth factor on DC cells. Northern blot analysis of DC cells reveals the presence of basic FGF mRNA species, and the DC cells coexpress multiple forms of basic FGF. Radioreceptor assays establish that the DC cells have high-affinity binding sites for basic FGF and proliferate in response to exogenous recombinant basic FGF. Furthermore, a conjugate between saporin (a ribosome-inactivating protein) and basic FGF, which is cytotoxic to cells possessing the basic FGF receptor, is also cytotoxic to DC cells. The possibility that basic FGF-saporin could be a potential therapeutic agent for prevention of recurrence of the disease after surgery is discussed.

Cell Division↗

PubMed1992

Acidic and basic fibroblast growth factors in adult rat heart myocytes. Localization, regulation in culture, and effects on DNA synthesis.

Basic fibroblast growth factor (bFGF) and acidic fibroblast growth factor (aFGF) are involved in the induction of embryonic mesoderm, angiogenesis, neuronal differentiation, and proliferation and survival of many cell types. In cardiac myocytes their roles are not well understood. Effects of fibroblast growth factors on reexpression of fetal actin genes have been reported. In freshly isolated adult rat cardiac myocytes, bFGF mRNA was not detectable by in situ hybridization, although the cells contained significant amounts of bFGF and aFGF as quantified by radioimmunoassays, mitogen assays with immunoneutralization, and Western blotting. After culturing, bFGF mRNA was detected (aFGF mRNA was not studied), and the cells contained 2.5-fold more bFGF and 60% more aFGF than freshly isolated cells. The FGFs were not found in conditioned medium. They were localized, especially in cultured cells, to the nucleus. Cultured myocytes bound fourfold more 125I-FGF than freshly isolated cells and expressed the fibroblast growth factor R-1 (flg) gene. The addition of bFGF or aFGF in serum-free medium to pure populations of myocytes (after 10 days in culture, at which time they are spread, beating, and multinucleated) led to increased thymidine incorporation. Expression of fibroblast growth factors and fibroblast growth factor receptors by adult cardiac myocytes that survive the shock and "dedifferentiation" of culturing may contribute to DNA synthesis and, by analogy, to other cell types, to regulation of ribosomal and actin genes, and to cell survival. These possibilities and their in vivo relevance will require further study.

Animals↗

PubMed1992

Basic fibroblast growth factor in Dupuytren's contracture.

Lesions excised from nine patients undergoing surgery for Dupuytren's contracture (DC) and three normal fascia were examined for the presence of the angiogenic protein basic fibroblast growth factor (basic FGF). Endothelial cell proliferation assays established basic FGF-like activity in extracts of DC. Western blotting confirmed the presence of an 18,000-dalton protein which was localized in the lesions by immunohistochemical staining. All of the cells implicated in the progression of the disease (endothelial cells, fibroblasts, and myofibroblasts) contain the growth factor. Endothelial cells within the narrowed or occluded vessels, as well as fibroblasts surrounding these vessels, stained intensely positive. In situ hybridization using an antisense probe for human basic FGF and its receptor's (FGFR-1) mRNA established the major difference between normal and DC tissues: their levels are significantly higher than in the normal tissues. Thus the cells in DC also express both basic FGF and FGFR-1, suggesting a potential autocrine/paracrine role for basic FGF in the pathogenesis of DC. This finding is thus the first description of a nontumoral proliferative disease that can be directly associated with increased basic FGF mRNA. The possibility that therapies can be developed on the basis that basic FGF and its receptor are expressed in DC is discussed.

Dupuytren Contracture↗

PubMed1989

Differential effects of heparin, fibronectin, and laminin on the phosphorylation of basic fibroblast growth factor by protein kinase C and the catalytic subunit of protein kinase A.

Basic fibroblast growth factor (FGF) is synthesized as a phosphoprotein by both bovine capillary endothelial and human hepatoma cells in culture. Because basic FGF is characterized by its high affinity for heparin and its association in vivo with the extracellular matrix, we examined the possibility that the phosphorylation of this growth factor by purified protein kinase C (PK-C) and the catalytic subunit of cAMP-dependent protein kinase-A (PK-A) can be modulated by components of the extracellular matrix. Heparin and other glycosaminoglycans (GAGs) inhibit the ability of PK-C to phosphorylate basic FGF. In contrast, heparin can directly increase the phosphorylation of basic FGF by PK-A. While fibronectin, laminin, and collagen IV have no effect on the ability of PK-C to phosphorylate basic FGF, they all can inhibit the effects of PK-A. Thus, there is a differential effect of extracellular matrix-derived proteins and GAGs on the phosphorylation of basic FGF. The enhanced phosphorylation of basic FGF that is mediated by heparin is associated with a change in the kinetics of the reaction and the identity of the amino acid targeted by this enzyme. The amino acids that are targeted by PK-C and PK-A have been identified by phosphopeptide analyses as Ser64 and Thr112, respectively. In the presence of heparin, basic FGF is no longer phosphorylated by PK-A at the usual PK-A consensus site (Thr112), but instead is phosphorylated at the canonical PK-C site (Ser64). Accordingly, heparin inhibits the phosphorylation of basic FGF by PK-C presumably by masking the PK-C dependent consensus sequence surrounding Ser64. Thus, when basic FGF is no longer phosphorylated by PK-A in the receptor binding domain (Thr112), it loses the increased receptor binding ability that characterizes PK-A phosphorylated basic FGF. The results presented here demonstrate three novel features of basic FGF. First, they identify a functional effect of the binding of heparin to basic FGF. Second, they establish that the binding of heparin to basic FGF can induce structural changes that alter the substrate specificity of protein kinases. Third, and perhaps most important, the results demonstrate the existence of a novel interaction between basic FGF, fibronectin, and laminin. Although the physiological significance of this phosphorylation is not known, these results clearly suggest that the biological activities of basic FGF are regulated by a complex array of biochemical interactions with the proteins, proteoglycans, and glycosaminoglycans present in the extracellular milieu and the cytoplasm.

Amino Acid Sequence↗