Biomedical subjects

Y Ohnishi

Publications and source records attributed to Y Ohnishi.

At least 37 records · Page 2Linked to original sources

PubMed2001

Structural features of a wheat plastome as revealed by complete sequencing of chloroplast DNA.

Structural features of the wheat plastome were clarified by comparison of the complete sequence of wheat chloroplast DNA with those of rice and maize chloroplast genomes. The wheat plastome consists of a 134,545-bp circular molecule with 20,703-bp inverted repeats and the same gene content as the rice and maize plastomes. However, some structural divergence was found even in the coding regions of genes. These alterations are due to illegitimate recombination between two short direct repeats and/or replication slippage. Overall comparison of chloroplast DNAs among the three cereals indicated the presence of some hot-spot regions for length mutations. Whereas the region with clustered tRNA genes and that downstream of rbcL showed divergence in a species-specific manner, the deletion patterns of ORFs in the inverted-repeat regions and the borders between the inverted repeats and the small single-copy region support the notion that wheat and rice are related more closely to each other than to maize.

DNA, Chloroplast↗

PubMed2001

Diesel exhaust-induced airway hyperresponsiveness in c-Ha-ras transgenic mice.

Recently the quantity of diesel exhaust (DE) emissions, which contain a variety of chemicals and can induce pulmonary carcinoma in animals, has been increasing in Japan. To assess the toxicity of DE, we evaluated airway hyperresponsiveness after exposure to DE in the rasH2 (CB6F1-TgHras2) mouse, which carries c-Ha-ras genes and shows marked sensitivity to treatment with various genotoxic carcinogens such as methylnitrosourea and dimethylbenzanthracene. We exposed rasH2 mice (n=18) and their nontransgenic littermates (n=19) to room air or 3 mg/m(3) DE for 4 weeks, measured their respiratory resistance (Rrs) during inhalation of acetylcholine (ACh; 0.005, 0.01, 0.02, 0.04, 0.08, 0.16, 0.31, 0.63, 1.28, 2.5, 5, or 10 mg/ml) for 2 min, and calculated the provocative ACh concentration needed to cause a 50% increase (PC(150)) in Rrs. At all doses of ACh, Rrs was significantly higher (P<0.05) in rasH2 mice exposed to DE than in those exposed to room air. In addition, Rrs in the DE-exposed rasH2 animals was significantly higher (P<0.05) at 0.16, 0.31, and 0.63 mg/ml ACh than in DE-exposed nontransgenic littermates. The PC(150) (mean+/-standard error) of DE-exposed rasH2 mice was 3.4+/-1.9 mg/ml, that in rasH2 mice exposed to room air was 10.6+/-2.5 mg/ml, and that in DE-exposed nontransgenic animals was 10.9+/-3.7 mg/ml. In conclusion, DE causes airway hyperresponsiveness in rasH2 mice and may induce the expression of c-Ha-ras genes.

Acetylcholine↗

PubMed2001

Association between a single-nucleotide polymorphism in the promoter of the human interleukin-3 gene and rheumatoid arthritis in Japanese patients, and maximum-likelihood estimation of combinatorial effect that two genetic loci have on susceptibility to the disease.

Genetic variants of interleukin-3 (IL-3), a well-studied cytokine, may have a role in the pathophysiology of rheumatoid arthritis (RA); but reports on this association sometimes conflict. A case-control study was designed to investigate association between RA and a single-nucleotide polymorphism (SNP) in the IL-3 promoter region. Comparison of cases of RA versus control individuals yielded a chi(2) value of 14.28 (P=.0002), with a genotype odds ratio of 2.24 (95% confidence interval [95%CI] 1.44-3.49). When female cases with earlier onset were compared with female control individuals, the SNP revealed an even more significant correlation, with chi2=21.75 (P=.000004) and a genotype odds ratio of 7.27 (95%CI 2.80-18.89). The stronger association that we observed in this clinically distinct subgroup (females with early onset), within a region where linkage disequilibrium was not significantly extended, suggested that the genuine RA locus should locate either within or close to the IL-3 gene. Combined genotype data on SNPs on eight other candidate genes were combined with our IL-3 results, to estimate relationships between pairs of loci and RA, by maximum-likelihood analysis. The utility of combining the genotype data in this way to identify possible contributions of various genes to this disease is discussed.

Age of Onset↗

PubMed2001

Smad translocation and growth suppression in lens epithelial cells by endogenous TGFbeta2 during wound repair.

To determine whether endogenous TGFbeta affects lens epithelial cells during repair after an anterior capsule injury in mice, we studied translocation of Smad proteins, which carry the TGFbeta signal from cell surface receptors to promoters in nuclei. We immunolocalized Smads in murine lenses at intervals up to 8 weeks following capsular injury. Effects of injecting TGFbeta neutralizing antibodies on Smad4 location and cell proliferation were examined at 24 hr after injury. Finally, we examined whether exogenous TGFbeta2 induced Smad nuclear translocation in murine lenses in organ culture. Cell proliferation was quantitated by 5-bromo-2'-deoxyuridine (BrdU) labelling. In uninjured lenses, Smads were located in the cytoplasm. In injured lenses, nuclear localization of Smads was observed in cells next to the capsular break from 8 to 24 hr after the injury, and was observed peripheral to the break at 48 hr. Nuclear Smads then continued to be observed occasionally in a minority of cells. Injection of antibodies neutralizing TGFbeta2, but not TGFbeta1 or TGFbeta3, inhibited Smad4 nuclear translocation and resulted in the appearance of BrdU-positive anterior epithelial cells. With the lenses in culture, transient nuclear localization of Smads occurred between 3 and 24 hr in response to continuous exposure to TGFbeta2. No nuclear translocation was seen at 48 hr. Endogenous TGFbeta2 affects lens cells during wound repair after anterior capsule injury, inhibiting lens cell proliferation during the early phase. Nuclear translocation of Smads in lens epithelial cells is transient even with continuous exposure to TGFbeta2.

Animals↗

PubMed2001

Expression of transcription factor AP-1 in rat lens epithelial cells during wound repair.

We examined the spatial and temporal expression patterns of proteins and mRNAs of the components of transcription factor activator protein 1 (AP-1) to examine the activation pattern of lens epithelial cells during lens wound repair following an anterior capsular injury. One eye of adult Wistar rats (n = 106) were used. After making a lens anterior capsule incision with a hypodermic needle, the affected eye was enucleated 0 and 30 min, 1, 3, 5, 8, 10, 15, 20, 24 hr after injury. Forty six globes were processed for in situ hybridization with oligonucleotide probes for c-fos, fosB, c-jun, junB and junD mRNAs, and 60 globes were immunohistochemically analysed using anti-c-Fos and anti-c-Jun antibodies. Normal lens epithelial cells expressed mRNA signals for junD, but not for c-fos, fosB, c-jun, and junB. mRNAs for c-fos, fosB, c-jun, and junB were detected in the whole lens epithelium from the vicinity to the wound to the equator from 30 min to 8 hr post-injury with their peaks after 30 min to 1 hr, but were no longer detected at 10 hr or later. Expression of c-fos mRNA in the equatorial lens cells was more marked than that of c-jun mRNA. Immunohistochemistry showed that c-Fos protein was expressed in the lens epithelial cells in both the anterior and equatorial regions of the injured lens from 1 to 10 hr after injury, and was no longer detected at 12 hr. C-Jun protein was detected only in the equatorial lens cells from 1 to 5 hr after injury, and was no longer detected at 8 hr. Lens epithelial cells except those in the equatorial region did not express c-Jun protein. These findings indicate that transcriptional activation of lens epithelial cells is initiated in the very early phase after the lens injury, i.e. 30 min post-injury, suggesting that AP-1 may play important roles in regulating lens cell behavior during lens wound repair in rats.

Animals↗

PubMed2001

Effects of dietary polyamine deficiency on Trypanosoma gambiense infection in rats.

Nishimura, K., Araki, N., Ohnishi, Y., and Kozaki, S. 2001. Effects of dietary polyamine deficiency on Trypanosoma gambiense infection in rats. Experimental Parasitology 97, 95-101. A diet deficient in polyamines decreases the availability of dietary polyamines. We used rats infected with the Wellcome strain of Trypanosoma gambiense to examine the effects of polyamine-deficient chow (PDC) on trypanosome proliferation and symptoms of infection. Rats fed PDC showed limited increase of trypanosome and symptoms of infection and limited loss of body weight and anemia. Survival in these rats was prolonged. Before infection, the heparinized plasma concentration of spermidine in the PDC-fed rats was lower than that in control rats fed with standard chow. After infection, the content of spermidine in red blood cells increased in the control rats, but was only slightly increased in PDC-fed rats. The content of spermidine in the trypanosomes after infection was low in the PDC-fed rats. Decreases in the polyamine content of trypanosomes limited their increase. These observations suggest that a reduction in dietary polyamines may help in the regulation of trypanosome infection.

Animal Feed↗

PubMed2001

Accumulation of latent transforming growth factor-beta binding protein-1 and TGF beta 1 in extracellular matrix of filtering bleb and of cultured human subconjunctival fibroblasts.

PURPOSE: To examine immunohistochemically whether extracellular matrix (ECM) of the filtering bleb and of cultured human subconjunctival fibroblasts contains latent TGF beta binding protein-1 (LTBP-1) and TGF beta. METHODS: An enucleated human eye that had undergone trabeculectomy and cultured human subconjunctival fibroblasts were processed for light microscopic immunohistochemistry. Antibodies against LTBP-1, collagen types, fibrillin-1 and TGF beta s were used. TGF beta 1 was located by detecting beta 1-latency associated peptide (LAP). RESULTS: LTBP-1, beta 1-LAP and fibrillin-1 were all located in the subepithelial ECM as well as in the basal epithelial cells of the conjunctiva over the filtering bleb. TGF beta 2 and beta 3 were immunolocated to epithelium and/or fibroblasts/keratocytes. ECM deposited in confluent fibroblast cultures was positive for beta 1-LAP, LTBP-1 and fibrillin-1, whereas sparse cells were negative. CONCLUSIONS: LTBP-1, beta 1-LAP and fibrillin-1 are co-localized to the ECM of the filtering bleb and of cultured conjunctival fibroblasts. Both conjunctival epithelium and fibroblasts are considered to be the source of TGF beta in healing bleb. ECM secreted by in vivo and in vitro subconjunctival fibroblasts may works as a scavenger or repository of TGF beta.

Carrier Proteins↗

PubMed2001

Effect of minoxidil on rabbit lens epithelial cell behavior in vitro and in situ.

BACKGROUND: Lens epithelial cell (LEC) proliferation and the associated production of extracellular matrix (ECM) are responsible for capsular opacification after cataract-IOL surgery. Minoxidil is an inhibitor of lysyl hydroxylase, an enzyme involved in procollagen hydroxylation. To evaluate the potential efficacy of minoxidil in inhibiting postoperative capsular opacification, we examined the effects of minoxidil on LEC behavior in cell and organ cultures. METHODS: We examined minoxidil effects on collagen production, migration and proliferation of cultured rabbit LECs as well as its ultrastructural effects, and also its effects on the cell population in organ-cultured capsular bag. RESULTS: No cytotoxicity was identified by MTT assay at the concentrations up to 3.0 mM of minoxidil, whereas it decreased the collagen production in LECs. Minoxidil also inhibited migration and proliferation of cells. Ultrastructural observation revealed the presence of dilated endoplasmic reticulum in LECs treated with minoxidil, indicating the accumulation of protein, probably underhydroxylated collagen precursors. The capsules cultured with minoxidil appeared less opaque than control specimens. On histological examination the numbers of cells on equatorial capsules were found to be significantly lower in minoxidil culture than in control culture. No lens cells were detected on the central posterior capsule of minoxidil culture, whereas they were seen in control. CONCLUSION: Minoxidil inhibited LEC migration and proliferation in vitro, as well as collagen secretion. Collagen secretion may be essential for LEC migration and proliferation. Minoxidil also attenuated repopulation of LECs on the inner surface of organ-cultured capsules. Minoxidil may be a potential inhibitor of postoperative capsular opacification.

Animals↗

PubMed2001

Surgical posterior vitreous detachment combined with gas/air tamponade for treating macular edema associated with branch retinal vein occlusion: retinal tomography and visual outcome.

PURPOSE: To assess the effectiveness of surgical posterior vitreous detachment (PVD) together with gas/air tamponade in treating visual impairment from macular edema associated with branch retinal vein occlusion (BRVO-macular edema). METHODS: A cohort study was conducted. To treat visual disturbance caused by BRVO-macular edema in 19 consecutive patients at a University Hospital, phacoemulsification, intraocular lens implantation, and vitrectomy were performed, together with gas/air tamponade. Patients were followed up postoperatively for 3-18 months. Foveal structure was defined using optical coherence tomography (OCT). Preoperative visual acuity, central retinal thickness, and interval between BRVO onset and operation were compared between patients with postoperative visual improvement and those without improvement. RESULTS: Ten patients recovered normal or near-normal foveal configuration, while nine patients did not. Mean postoperative visual acuity in the former group of patients was significantly higher than in the latter. Mean foveal retinal thickness decreased significantly after the operation. The interval from onset of BRVO until operation was significantly shorter in patients with improved postoperative vision than in other patients, and patients operated on within 11 months had significantly increased postoperative visual acuity. CONCLUSIONS: Surgical PVD and gas/air tamponade appears effective in treating BRVO-macular edema, although relatively short duration from disease onset until operation is critical for improvement of vision. When a good postoperative foveal contour is seen, it seems to be associated with better visual outcome.

Adult↗

PubMed2001

High-density single-nucleotide polymorphism (SNP) map in the 96-kb region containing the entire human DiGeorge syndrome critical region 2 (DGCR2) gene at 22q11.2.

We constructed a high-density single-nucleotide polymorphism (SNP) map in the 96-kb region containing the DiGeorge syndrome critical region 2 (DGCR2) gene at chromosome 22q11.2, a human counterpart of mouse seizure-related gene SEZ-12. A total of 102 SNPs were isolated from the region by systematic screening among 48 Japanese individuals: 9 SNPs in the 5' flanking region, 3 in the 5' untranslated region, 2 in the coding regions, 77 in introns, 7 in the 3' untranslated region, and 4 in the 3' flanking region. By a comparison of our data with SNPs deposited in the dbSNP database in the National Center for Biotechnology Information, 80 SNPs (78.4%) were considered to be novel. The ratio of transition to transversion was 3.08:1. In addition, eight other types of genetic variations (one GA dinucleotide polymorphism and seven insertion/deletion polymorphisms) were discovered. The high-resolution map that we constructed will be a useful resource for analyzing gene scans of complex diseases mapped to this local segment on chromosome 22.

3' Untranslated Regions↗

PubMed2001

A high-throughput SNP typing system for genome-wide association studies.

One of the most difficult issues to be solved in genome-wide association studies is to reduce the amount of genomic DNA required for genotyping. Currently available technologies require too large a quantity of genomic DNA to genotype with hundreds or thousands of single-nucleotide polymorphisms (SNPs). To overcome this problem, we combined the Invader assay with multiplex polymerase chain reaction (PCR), carried out in the presence of antibody to Taq polymerase, as well as using a novel 384-well card system that can reduce the required reaction volume. We amplified 100 genomic DNA fragments, each containing one SNP, in a single tube, and analyzed each SNP with the Invader assay. This procedure correctly genotyped 98 of the 100 SNP loci examined in PCR-amplified samples from ten individuals: the genotypes were confirmed by direct sequencing. The reproducibility and universality of the method were confirmed with two additional sets of 100 SNPs. Because we used 40 ng of genomic DNA as a template for multiplex PCR, the amount needed to assay one SNP was only 0.4 ng; therefore, theoretically, more than 200,000 SNPs could be genotyped at once when 100 microg of genomic DNA is available. Our results indicate the feasibility of undertaking genome-wide association studies using blood samples of only 5-10 ml.

Alleles↗

PubMed2001

Lens epithelial cell regeneration of a capsule-like structure during postoperative healing in rabbits.

PURPOSE: To determine whether lens epithelial cells (LECs) can regenerate the lens capsule during healing after lens extraction and intraocular lens (IOL) implantation. SETTING: Department of Ophthalmology, Wakayama Medical College, Japan. METHODS: Extracapsular lens extraction and IOL implantation were performed in 5 adult albino rabbits. Lens capsules were examined histologically and immunohistochemically 3 and 5 months later. RESULTS: Lens epithelial cells proliferated and regenerated lens fibers within the capsular bag. A multilayered homogenous capsule-like structure was present in the equatorial region. The structures contained type IV collagen but not type I collagen. CONCLUSION: Lens epithelial cells can regenerate lens capsule-like structures during healing after lens extraction. Postoperative LECs without phenotypic conversion to a fibroblastic type may produce this structure.

Animals↗

PubMed2001

Comparison of Scheimpflug images of posterior capsule opacification and histological findings in rabbits and humans.

PURPOSE: To compare the posterior capsule opacification in Scheimpflug photographic images produced by an electronic anterior eye segment analysis system with the histopathological findings in rabbits and humans. SETTING: Department of Ophthalmology, Wakayama Medical College, Japan. METHODS: Opacified posterior capsules were photographed using the EAS-1000 system (Nidek) and were then extracted during vitreous surgery for proliferative diabetic retinopathy or proliferative vitreoretinopathy in 2 patients. In rabbits, phacoemulsification and aspiration (PEA) with intraocular lens (IOL) implantation was performed. The IOL was implanted in the bag or in the sulcus. After intervals of healing, the posterior capsule was photographed with the EAS-1000 and the animals were then killed. In both clinical and experimental specimens, the posterior capsule was processed for light microscopic histology and immunohistochemistry. RESULTS: Opacified human capsules were well imaged by the EAS-1000. Histology showed that lens epithelial cells proliferated with and without an accumulation of extracellular matrix. Details such as rolling of the capsulotomy edge were seen well. Regenerated lens fibers of Soemmering's ring were seen as a mass within the capsule. In the rabbit model, Scheimpflug images accurately represented the capsules as they appeared histologically. CONCLUSION: The EAS-1000 system provided faithful, relatively high-resolution images that corresponded to the histologic findings in the posterior capsules after PEA-IOL surgery in humans and rabbits.

Aged↗

PubMed2001

Effects of antiinflammatory drugs on migration of the rabbit corneal epithelium.

PURPOSE: To evaluate and compare the effects of diclofenac sodium 0.1% and betamethasone phosphate 0.1% on corneal wound healing. SETTING: Department of Ophthalmology, Wakayama Medical College, Wakayama, Japan. METHODS: Using the method described by Nishida et al., corneal epithelial spreading was measured in vitro in a rabbit corneal block in the presence or absence of 2 antiinflammatory agents at various doses. RESULTS: At clinical doses (1 microg/mL and 10 microg/mL), the drugs did not suppress migration of the corneal epithelium. At high doses (20 microg/mL, 50 microg/mL, and 100 microg/mL), they did inhibit the migration. There was no between-group difference in corneal epithelial migration at clinical doses. At high doses, corneal epithelial migration was inhibited in the diclofenac sodium group compared with the betamethasone group. CONCLUSIONS: At clinical doses, diclofenac sodium and betamethasone did not inhibit corneal epithelial migration. However, these drugs should be prescribed cautiously in patient with high-risk diseases such as diabetes mellitus and glaucoma.

Animals↗

PubMed2001

Evaluation of cellular adhesions on silicone and poly(methyl methacrylate) intraocular lenses in monkey eyes: an electron microscopic study.

PURPOSE: To assess the biocompatibility of intraocular lens (IOL) material by studying the number of cells adhering to IOLs in monkey eyes. SETTING: Department of Ophthalmology, Kyushu University, Fukuoka, Japan. METHODS: Silicone or poly(methyl methacrylate) (PMMA) IOL implantation was performed in 21 monkeys. One eye of each animal had surgery. The IOL-implanted eyes were enucleated 1, 2, 3, 5, and 7 days and 1, 3, 4, 5, and 9 months after the procedure. One eye was studied at each time. Cells on the anterior IOL surface were photographed using a scanning electron microscope, counted and assessed with NEC, Graphtec, and Nikon equipment, and then observed using a transmission electron microscope. RESULTS: Leukocytes, macrophages, and giant cells were found on the anterior IOL surface. Numerous cells were observed on the PMMA IOLs in the early postoperative period; they gradually decreased. Few cells were seen on the silicone IOLs during the course of the study. The giant cells became larger during the postoperative period. CONCLUSION: The foreign-body reaction to silicone IOLs in monkey eyes was less than that to PMMA IOLs.

Animals↗

PubMed2001

Relationship between partial inhibition of glycolysis and hemolysis after induction of gametocytogenesis in synchronous cultures of Plasmodium falciparum.

In the present study, the low molecular-weight fraction of the culture supernatant of anti-Plasmodium falciparum antibody-producing hybridoma cells (HybSL) was used in synchronous culture with P. falciparum FVO strain. When synchronous cultures were treated with HybSL solution on day 5, gametocytogenesis was also induced. Gametocytes were consistently found from the third day after treatment and reached a peak on the fourth day. An increase in pH and hemoglobin concentrations and decrease in lactate concentrations were observed on the first day after treatment. These phenomena suggested that HybSL solution partially inhibited glycolysis of erythrocytes parasitized with schizonts and resulted in hemolysis of infected erythrocytes. On the other hand, the production of gametocytes did not increase in cultures treated with HybSL solution on day 4 of synchronous cultures in which ring forms were plentiful. Most ring forms were not killed by HybSL solution and quickly developed to trophozoites and schizonts rather than gametocytes. Consequently, it is assumed that ring forms on day 4 of synchronous cultures have finished differentiation into the asexual stage. The conversion of asexual parasites to gametocytes may be triggered only when late-stage trophozoites or early-stage schizonts are treated with HybSL solution.

Animals↗

PubMed2001

Inhibitory effects of brefeldin A, a membrane transport blocker, on the bradykinin-induced hyperpolarization-mediated relaxation in the porcine coronary artery.

1. To elucidate the mechanism of the relaxation mediated by endothelium-derived hyperpolarizing factors (EDHFs), the effect of brefeldin A, a membrane transport blocker, on cytosolic Ca(2+) concentration ([Ca(2+)]i) and tension was determined in the porcine coronary arterial strips. We also examined the effect of brefeldin A on [Ca(2+)]i in the endothelial cells of the porcine aortic valve. 2. In the presence of 10 microM indomethacin and 30 microM N(G)-nitro-L-arginine (L-NOARG), both bradykinin and substance P induced a transient decrease in [Ca(2+)]i and tension in arterial strips contracted with 100 nM U46619 (thromboxane A2 analogue). A 6 h pre-treatment with 20 microg ml(-1) brefeldin A abolished the bradykinin-induced relaxation, while it had no effect on the substance P-induced relaxation. 3. In the absence of indomethacin and L-NOARG, brefeldin A had no effect on the bradykinin-induced relaxation during the contraction induced by U46619 or 118 mM K(+). 4. The indomethacin/L-NOARG-resistant relaxation induced by bradykinin was completely inhibited by 3 mM tetrabutylammonium (non-specific Ca(2+)-activated K(+) channel blocker), while that induced by substance P was not inhibited by 3 mM tetrabutylammonium or 1 mM 4-aminopyridine (voltage-dependent K(+) channels blocker) alone, but completely inhibited by their combination. 5. Brefeldin A had no effect on the [Ca(2+)]i elevation in endothelial cells induced by bradykinin or substance P. 6. In conclusion, bradykinin produce EDHF in a brefeldin A-sensitive mechanism in the porcine coronary artery. However, this mechanism is not active in a substance P-induced production of EDHF, which thus suggests EDHF to be more than a single entity.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2001

The A-factor regulatory cascade and cAMP in the regulation of physiological and morphological development in Streptomyces griseus.

In the A-factor regulatory cascade leading to the onset of streptomycin biosynthesis and aerial mycelium formation in Streptomyces griseus, the A-factor receptor protein (ArpA) serves as a DNA-binding repressor and A-factor releases the repression by binding to ArpA and dissociating it from the DNA. Mutants defective in arpA therefore produce streptomycin and aerial hyphae in the absence of A-factor. A gene that inhibits streptomycin production and aerial hyphae formation in an arpA mutant was cloned on a high-copy-number plasmid and found to encode a eukaryotic-type adenylate cyclase (CyaA). Consistent with this, an exogenous supply of cAMP at high concentration almost abolished streptomycin production and aerial hyphae formation. On the other hand, cAMP at lower concentrations stimulated or accelerated these developmental processes. The effects of cAMP were detectable only in arpA mutants, and not in the wild -type strain; an exogenous supply of cAMP or cyaA disruption in the wild-type strain caused almost no effect on these phenotypes. Thus the effects of cAMP became apparent only in the arpA-defective background. cAMP at high concentrations inhibited stringent response factor ppGpp production, which is important for the onset of antibiotic biosynthesis. cAMP also influenced the timing of tyrosine phosphorylation of more than nine proteins. These findings show that a cAMP regulatory relay for physiological and morphological development functions in a concerted and interdependent way with other signal transduction pathways.

4-Butyrolactone↗