Search PubMed⌕ Search

Biomedical subjects

T Fujioka

Publications and source records attributed to T Fujioka.

At least 19 recordsLinked to original sources

The auditory evoked magnetic fields to very high frequency tones.

We studied the auditory evoked magnetic fields (AEFs) in response to pure tones especially at very high frequencies (from 4000 Hz to 40,000 Hz). This is the first systematic study of AEFs using tones above 5000 Hz, the upper audible range of humans, and ultrasound. We performed two experiments. In the first, AEFs were recorded in 12 subjects from both hemispheres under binaural listening conditions. Six types of auditory stimulus (pure tones of five different frequencies: 4000 Hz, 8000 Hz, 10,000 Hz, 12,000 Hz, 14,000 Hz, and a click sound as the target stimulus) were used. In the second experiment, we used 1000 Hz, 15,000 Hz, and two ultrasounds with frequencies of 20,000 Hz and 40,000 Hz. The subjects could detect all stimuli in the first experiment but not the ultrasounds in the second experiment. We analyzed N1m, the main response with approximately 100 ms in peak latency, and made the following findings. (1) N1m responses to the tones up to 12,000 Hz were clearly recorded from at least one hemisphere in all 12 subjects. N1m for 14,000 Hz was identified in at least one hemisphere in 10 subjects, and in both hemispheres in six subjects. No significant response could be identified to ultrasounds over 20,000 Hz. (2) The amplitude of the N1m to the tones above 8000 Hz was significantly smaller than that to 4000 Hz in both hemispheres. There was a tendency for the peak latency of the N1m to be longer for the tones with higher frequencies, but no significant change was found. (3) The equivalent current dipole (ECD) of the N1m was located in the auditory cortex. There was a tendency for the ECD for the tones with higher frequencies to lie in more medial and posterior areas, but no significant change was found. (4) As for the interhemispheric difference, the N1m amplitude for all frequency tones was significantly larger and the ECDs were estimated to be located more anterior and medial in the right hemisphere than the left. The priority of the right hemisphere, that is the larger amplitude, for very high frequency tones was confirmed. (5) The orientation of the ECD in the left hemisphere became significantly more vertical the higher the tones. This result was consistent with previous studies which revealed the sensitivity of the frequency difference in the left hemisphere. From these findings we suggest that tonotopy in the auditory cortex exists up to the upper limit of audible range within the small area, where the directly air-conducted ultrasounds are not reflected.

Acoustic Stimulation↗

Drug combinations with amoxycillin reduce selection of clarithromycin resistance during Helicobacter pylori eradication therapy.

This study investigated the relationship between the drug combinations of the eradication regimens and the prevalence of acquired resistance to clarithromycin. Of 540 patients treated with anti-Helicobacter pylori regimens containing clarithromycin, 55 patients (31 males, mean age, 45.6 years) with failed eradication of H. pylori that was susceptible to clarithromycin before treatment were included. The E test was used to test for susceptibility to clarithromycin (minimum inhibitory concentration (MIC) <1 mg/l). Of the 55 patients, 33 (60.0%) developed clarithromycin resistance after failed eradication. Of the dual therapies, the combination of a proton pump inhibitor (PPI) and clarithromycin resulted in 88.9% (8/9) of the patients acquiring clarithromycic-resistance. With the triple therapies, the percentages of patients acquiring clarithromycin resistant strains after using a PPI+clarithromycin+amoxycillin or a PPI+clarithromycin+metronidazole were 38.7% (12/31) and 90.0% (9/10), respectively (P<0.01). These data suggest that regimens containing amoxycillin may prevent the selection of secondary clarithromycin resistance.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Sensitivity of biopsy site in evaluating regression of gastric atrophy after Helicobacter pylori eradication treatment.

BACKGROUND: Helicobacter pylori infection is a major cause of the progress of gastric glandular atrophy, a high-risk background factor in the development of gastric cancer. Regression of gastric atrophy is critical to prevention of cancer by H. pylori eradication treatment. However, it is controversial whether gastric atrophy regresses after H. pylori eradication. AIM: To determine the most sensitive and appropriate biopsy site for evaluation of regression of atrophy after treatment. SUBJECTS AND METHODS: Thirty-eight patients who showed regression of gastric atrophy in histology after treatment were investigated. Four biopsy specimens from the lesser and greater curvatures in the antrum and corpus were evaluated before and after treatment according to the Updated Sydney System. RESULTS: Regression of atrophy after treatment was seen in 30 of 38 biopsy specimens from the lesser curvature of the corpus (79%), and this site was most sensitive. Odds ratio of this site to the others was 8.28. Regression of atrophy in this site was observed at 12.2 months in the younger patients and 15.9 months in the elder patients. CONCLUSION: Biopsy sampling from the lesser curvature of the corpus is the most sensitive and appropriate for evaluation of regression of gastric atrophy after H. pylori eradication treatment.

Adult↗

Eradication rates of clarithromycin-resistant Helicobacter pylori using either rabeprazole or lansoprazole plus amoxicillin and clarithromycin.

BACKGROUND: The resistance of Helicobacter pylori to clarithromycin has become one of the primary reasons for eradication failure. AIM: To compare the eradication rates of triple therapy using amoxicillin (A), clarithromycin (C) and rabeprazole (R) or lansoprazole (L) against clarithromycin-sensitive and clarithromycin-resistant strains. METHODS: Two hundred and ninety-five patients were randomly divided into four groups and treated for 1 week: 147 cases were treated with RAC, i.e. 49 cases with R20C400 (10 mg R + 750 mg A + 200 mg C, twice daily), 48 cases with R40C400 (20 mg R + 750 mg A + 200 mg C, twice daily) and 50 cases with R40C800 (20 mg R + 750 mg A + 400 mg C, twice daily); 148 cases with treated with LAC (30 mg L + 750 mg A + 200 mg C, twice daily). RESULTS: According to intention-to-treat and per protocol analyses, the eradication rates were 88% and 91% with RAC and 78% and 81% with LAC; the eradication rates with R20C400, R40C400 and R40C800 were 94%, 81% and 86%, respectively, in the intention-to-treat analysis. In addition, the eradication rates for clarithromycin-sensitive strains with RAC and LAC were 98% and 89%, respectively, and for clarithromycin-resistant strains with RAC and LAC were 8.1% and 0%, respectively. CONCLUSIONS: The eradication rate was significantly higher with RAC than LAC. The eradication rate for clarithromycin-resistant strains was low in both groups, and an improved eradication rate could not be achieved by changing the dose of clarithromycin or proton pump inhibitor.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Allelotype analysis of gallbladder carcinoma associated with anomalous junction of pancreaticobiliary duct.

Anomalous junction of pancreaticobiliary duct (AJPBD) patients has an increased risk of gallbladder and bile duct carcinomas. However, the relevance of carcinoma with AJPBD is not fully clarified. We performed analysis of loss of heterozygosity (LOH) at p53 locus and immunohistochemistry of p53 and K-ras gene mutation in five cases of gallbladder carcinoma associated with AJPBD. LOH of p53 locus and overexpression of p53 were detected in two out of five (40%) and five out of five (100%), respectively, in the present study. K-ras gene mutation at codon 12 and 13 was not detected (0%, 0/5). These results suggest that aberrations of p53 are involved in carcinogenesis of gallbladder carcinoma associated with AJPBD. Next, in order to find the genetic events besides K-ras mutation and overexpression of mutant p53 in this disease, LOH analysis was performed using 72 microsatellite markers. High frequency of allelic loss (> 50%) was found on 2p (81.8%), 4p (50%), 4q (50%), 8q (60%), 9q (50%), 10p (50%), 14p (60%), 14q (50%), 16p (60%), 19p (50%), 21p (50%) and Xp (66.6%). The highest deletion regions on chromosome 2p24 (3/3, 100%), 14q22 (3/4, 75%) and 21q22 (3/4, 75%) were found. The present study suggests that gallbladder carcinoma associated with AJPBD has high frequent allelic loss and has two new regions which may harbor putative tumor suppressor genes.

Aged↗

Effect of methylprednisolone on the kinetics of cytokines and liver function of regenerating liver in rats.

The participation of cytokines in the early stage mechanism of hepatocyte proliferation has already attracted attention. We investigated the effect of methylprednisolone (MDS), which inhibits the inflammatory response, given before and after a 70% partial hepatectomy in rats on the kinetics of tumor necrosis factor-alpha and Interleukin-6, liver cell function and the rate of liver regeneration. Serum Interleukin-6 levels of the MDS groups were significantly lower than those of the control group. Serum alanine aminotransferase, aspartate aminotransferase and hyaluronic acid levels were also significantly decreased, however, the serum albumin level showed high values in the MDS groups. In the MDS groups, MIB-5 labeling indices, a novel antibody reactive with the equivalent Ki-67 protein, which detects immunohistochemically all active parts of the cell cycle in the rat liver, were more pronounced than in the control group at an earlier time. However, in regard to 5-bromo-2-deoxyuridine (BrdU), there were no significant differences among the three groups. There were no differences in residual liver weight/body weight between the three groups after 336 h. In our study, MDS administration before or after a 70% partial hepatectomy decreased serum Interleukin-6 levels, and inhibited hepatic dysfunction. Therefore, we considered that beneficial effects of physiological doses of MDS in the peri-operative period should be confirmed in humans.

Journal Article↗

Endothelial dysfunction and decreased exercise tolerance in interferon-alpha therapy in chronic hepatitis C: relation between exercise hyperemia and endothelial function.

BACKGROUND: We previously reported that reversible endothelial dysfunction is caused by interferon-alpha therapy (IFN) in patients with chronic hepatitis C. In experimental studies, limb blood flow during exercise is reported to be dependent on endothelium-derived nitric oxide. HYPOTHESIS: The purpose of this study was to confirm the effect of IFN on endothelial function and to investigate whether exercise hyperemia is dependent on endothelial function in humans. METHODS: We performed symptom-limited exercise treadmill testing and measured flow-mediated vasodilation (FMD, endothelium-dependent vasodilation) and sublingual glyceryl-trinitrate-induced dilation (GTN-D, 0.3 mg, endothelium-independent vasodilation) in the brachial artery by using high-resolution ultrasound in 10 patients with chronic active hepatitis C (age 53 +/- 11 years, 2 men, 8 women) before and immediately after administration of recombinant interferon 2b (10 million U/day) for 4 weeks. RESULTS: There were no significant abnormal findings in any patients in routine studies of 24-h ambulatory electrocardiogram monitoring, two-dimensional echocardiography, and exercise treadmill testing both before and after treatment. Leg fatigue and exhaustion were the reasons for termination of exercise treadmill testing in each patient. Pressure rate product was calculated at rest and peak exercise. Interferon-alpha therapy significantly (p<0.05) decreased FMD (6.8 +/- 3.1 vs. 1.9 +/- 2.6%), exercise treadmill testing tolerance time (437 +/- 89 vs. 395 +/- 62 s) and peak pressure rate product (283 +/- 41 vs. 241 +/- 47 mmHg x beats/min x 10(-2)), but not GTN-D (13.4 +/- 5.4 vs. 17.0 +/- 5.5%). The change of FMD due to IFN significantly and highly correlated with exercise treadmill testing tolerance time (r = 0.86, p<0.001), but not with change of peak pressure rate product, suggesting that FMD is more closely related to the condition of the peripheral circulation than is cardiac performance. CONCLUSION: These results suggest that IFN in patients with chronic hepatitis C impairs endothelial function and exercise tolerance, and that endothelial function might be at least partly involved in exercise hyperemia in humans.

Adult↗

Modulation of susceptibility and resistance to an autoimmune model of multiple sclerosis in prototypically susceptible and resistant strains by neutralization of interleukin-12 and interleukin-4, respectively.

Experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, is mediated by Th1 cells. The major Th1 inducer, IL-12, enhances EAE, while its blockade suppresses it. IL-4 suppresses EAE. Here, we determined IFN-gamma and IL-4 production by myelin basic protein-stimulated lymphocytes from prototypically EAE-susceptible SJL/J and EAE-resistant BALB/c mice, 9 days after immunization with spinal cord homogenate. While lymphocytes from SJL/J mice produce IFN-gamma and no IL-4, lymphocytes from BALB/c mice produce IL-4 and no IFN-gamma. Since early endogenous production of IL-12/IFN-gamma or IL-4 is linked to Th1 or Th2 responses, respectively, we determined whether neutralization of IL-12 or IL-4 at immunization modifies susceptibility or resistance to EAE. SJL/J mice given neutralizing anti-IL-12 mAb are protected from EAE. BALB/c mice given neutralizing anti-IL-4 mAb develop EAE, while those treated with control antibody remain resistant. These studies confirm the pivotal role of IL-12 in EAE development and show that endogenous IL-4 is important for determining the genetic resistance to EAE.

Animals↗

The effects of ovariectomy and female sex hormones on hepatic metallothionein-I gene expression after injection of cadmium chloride in mice.

Metallothioneins (MTs) have a low molecular weight and have been considered to be important metal-binding proteins in defense from cadmium (Cd) toxicity in animals. These proteins are known to be induced by the injection of heavy metals such as Cd. Previously, we developed the measurement of the MT mRNA expression by the RT-PCR method. In this study, to clarify the relation between Cd-induced MT-I mRNA expression and female sex hormones in liver, we investigated the influences of the ovariectomy and female sex hormones on hepatic MT-I mRNA expression after Cd injection, and also investigated the effects of aging on hepatic MT-I mRNA expression in mice after Cd injection. We analysed the MT-I mRNA expression by the RT-PCR method. Cd-induced MT-I mRNA expression in ovariectomized mice was more than that in sham-operated mice (9 weeks old). Both 17 beta -estradiol and progesterone reduced the Cd-induced MT-I mRNA expression in ovariectomized mice (9 weeks old). Moreover, the MT-I mRNA expression in male mice was more than that of females (9 weeks old). However, the sex difference in the gene expression was not found in younger (4 weeks old) or older (46 weeks old) mice. These results suggest that the expression of hepatic MT-I mRNA after Cd injection is influenced by female sex hormones.

Animals↗

Lethal adenovirus infection in a patient who had undergone nonmyeloablative stem cell transplantation.

We present a case of adenovirus (ADV) infection in a patient who had undergone nonmyeloablative stem cell transplantation (NST). A 50-year-old man with chronic myelogenous leukemia in the second chronic phase underwent NST from an HLA 2-loci-mismatched sibling. ADV hemorrhagic cystitis developed and progressed to lethal pneumonia. ADV was isolated from urine, bronchoalveolar lavage fluid, and postmortem specimens of kidney and liver. Because there are few reports of lethal pneumonia associated with ADV in Japan, we present the case and discuss the cause of and therapy for the infection.

Adenoviridae Infections↗

Anti-transforming growth factor-beta1 antibody transiently enhances DNA synthesis during liver regeneration after partial hepatectomy in rats.

The regulation of liver regeneration after partial hepatectomy (PHx) is complex and involves many different cytokines. We investigated the role of one of these, transforming growth factor-beta1 (TGF-beta1), an inhibitor of liver regeneration, in a Wistar male rat model, in which anti-TGF-beta1 antibody was injected immediately or 24 h after 70% PHx. Livers from treated animals contained an increased number of cells in S phase, according to 5-bromo-2'-deoxyuridine (BrdU) labeling 36 h after PHx. Antibody administration 24 h after PHx resulted in the highest peak of proliferation; moreover, peak MIB-5 labeling was also observed at that time. However, neither residual liver-weight-to-body-weight ratios nor regeneration rates differed significantly between any of the animals. Therefore, we also measured levels of serum TGF-beta1 and hepatocyte growth factor (HGF; an activator). With antibody administration at 0 or 24 h, TGF-beta1 levels were diminished at 24 or 36 h as compared with levels in control rats, but then rebounded, reaching a delayed peak at 48 or 72 h after PHx, respectively. Interestingly, there were also similar trends in HGF levels. These results indicate that TGF-beta1 may inhibit the G1 checkpoint, and serum TGF-beta1 concentration may influence HGF to regulate liver regeneration and to maintain homeostasis of proliferation after PHx.

Analysis of Variance↗

Prevalence of Helicobacter pylori infection and correlation between severity of upper gastrointestinal lesions and H. pylori infection in Japanese patients with Crohn's disease.

BACKGROUND: The prevalence of Helicobacter pylori infection in Crohn's disease (CD) patients was investigated to determine whether the presence and severity of gastroduodenal lesions were related to H. pylori infection. METHODS: Infection rates were compared between CD group (n = 90) and the control group (n = 525). Correlations between endoscopically detected lesions and H. pylori positive rates were investigated. The relationship between drug therapy and the prevalence of H. pylori infection was also analyzed. RESULTS: H. pylori-positive rate of the 90 CD patients attending our clinic was 16.7%, significantly lower than the rate in healthy controls (40.2%) (P = 0.0001). The involvement of H. pylori infection in the gastroduodenal lesions of CD patients was also examined. The prevalence of gastroduodenal lesions in all CD patients was high, 92.2%. The lesions observed included ulcers, erosion, and "bamboo joint-like lesions" of the stomach, and ulcers, erosion, stenosis, and elevated lesions of the duodenum. None of these lesions were found to be related to H. pylori infection. However, H. pylori infection was found to exacerbate gastric ulcers (P = 0.036). The analysis of a possible relationship between a history of drug therapy and the low prevalence of H. pylori infection in CD patients showed that the prevalence of H. pylori infection was significantly lower in patients who had received antibiotics for 2 weeks or more (P = 0.002). CONCLUSIONS: The results suggest that H. pylori infection is essentially unrelated to the gastroduodenal lesions observed in CD. It seems likely, however, that H. pylori infection may exacerbate gastric ulcers and that H. pylori can be eradicated by prolonged use of antibiotics.

Adolescent↗

Modulating effects of prenatal stress on hyperthermia induced in adult rat offspring by restraint or LPS-induced stress.

The present study was carried out to investigate the effects of prenatal stress on stress-induced hyperthermia in adult rats. Prenatal stress was administered daily for 3 days (embryonic days 15-17) by restraining pregnant rats in a small cage either for 30 or 240 min. After birth, foster mothers raised the pups. Offspring were tested at 9-10-weeks-old. Changes in body temperature and in the plasma concentrations of corticosterone, norepinephrine (NE), and epinephrine (Epi) induced by restraint or lipopolysaccharide (LPS)-induced stress were examined. By comparison with the prenatally nonstressed control group, the 240-min stress group showed a significantly lower hyperthermia in response to restraint stress but a higher fever after injection of LPS. The 30-min stress group showed similar alterations in these hyperthermic responses but did not reach significance. Both the restraint stress and the injection of LPS evoked greater increases in the plasma level of corticosterone in the 240-min stress group than in the control group. Although restraint stress induced significant increases in NE and Epi in the control and 30-min stress groups, the plasma levels of these catecholamines did not increase in the 240-min stress group. These results demonstrate for the first time that prenatal stress has opposite effects on the hyperthermic responses to restraint and LPS injection, suggesting that different mechanisms underlie the modulating effects of prenatal stress on the responses to the two types of stressors.

Animals↗

An ellagic compound and iridoids from Cornus capitata root cultures.

An ellagic acid derivative, 3,3'-di-O-methylellagic acid 4-(5"-acetyl)-alpha-L-arabinofuranoside, and two iridoid glucosides, 6alpha-dihydrocornic acid and 6beta-dihydrocornic acid, were isolated from Cornus capitata adventitious roots cultured in Murashige-Skoog (Murashige, T., Skoog, F., 1962. A revised medium for rapid growth and bioassays with tobacco tissue cultures. Physiol. Plant. 15, 473-487) liquid medium containing 10 microM CuSO(4). Three known related metabolites, i.e. stenophyllin H1, dihydrocornin and cornin were also produced in the root cultures. The chemical structures were characterized by analysis of spectroscopic data.

Ellagic Acid↗

Mild prenatal stress enhances learning performance in the non-adopted rat offspring.

The present study was designed to investigate whether mild stress during pregnancy affects offspring behaviors, including learning performance. Prenatal stress was induced by short-lasting, mild restraint stress, which had previously been shown to facilitate the morphological development of fetal brain neurons. Adult offspring whose dams had been restrained in a small cage for 30min daily from gestation day 15 to 17 showed enhanced active avoidance and radial maze learning performance. In addition, the prenatally stressed rats showed weaker emotional responses than unstressed control, as indicated by decreases both in ambulation upon initial exposure to an open field and in Fos expression in the amygdala induced by physical stress. The observed effects of prenatal stress on learning performance and emotional behavior were attenuated by foster rearing by unstressed dams. Fos expression in the hypothalamic paraventricular nucleus following physical stress and corticosterone secretion during physical and psychological stress did not differ between the prenatally stressed and unstressed control rats. From these results we suggest that mild prenatal stress facilitates learning performance in the adult offspring. The enhancement of learning performance appears to be accompanied by reduced emotionality, but not by any apparent alterations in hypothalamic-pituitary-adrenal responses. In addition, the observation of differential behaviors in the adopted and non-adopted animals supports the notion that the postnatal environment modifies the behavioral effects of prenatal stress.

Amygdala↗

A case of agranulocytosis associated with severe acute hepatitis B.

A 29-year-old male patient with acute hepatitis B developed agranulocytosis about 2 months after the clinical onset of the hepatitis. Bone marrow examination showed hypercellularity and maturation arrest of myeloid leukogenesis at the stage of metamyelocyte. Anti-neutrophil antibody was negative. Since the patient did not show spontaneous recovery for 2 months, the patient received granulocyte-colony stimulating factor, but the therapy was a very short course because he had an elevation of temperature and nausea. Sixty-eight days after admission, he was started on lithium carbonate at a dose of 600 mg per day. About 3 weeks later, peripheral granulocyte counts had recovered to normal level.

Journal Article↗

Involvement of insulin receptor substrates in epidermal growth factor induced activation of phosphatidylinositol 3-kinase in rat hepatocyte primary culture.

Short-term incubation of adult rat hepatocytes with epidermal growth factor (EGF) caused tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2 when the cells had been submitted to primary culture from 1-18 h. Tyrosine-phosphorylated IRS-1 and IRS-2 bound to the regulatory subunit (p85) of phosphatidylinositol (PtdIns) 3-kinase, thereby activating the enzymic activity. Tyrosine phosphorylation of the IRSs and activation of PtdIns 3-kinase in 3 h cultured hepatocytes both proceeded similarly to the same actions of insulin; the activation was rapid and transient, with peak values at 15-30 s and with similar EC(50)s in the nM range in both cases. A possible involvement of insulin receptors in these insulin-like actions of EGF was excluded by the following three lines of evidence. Insulin caused tyrosine phosphorylation of the insulin receptor beta-subunit but EGF did not. In contrast, the EGF receptor was phosphorylated by EGF, but the insulin receptor was not. The actions of EGF, but not those of insulin, were inhibited by AG1478, a selective inhibitor of EGF receptor tyrosine kinase. Cultured hepatocytes exposed to insulin or insulin-like growth factor-I (IGF-I) for a short period responded to the subsequent addition of EGF, whereas EGF-treated cells responded to insulin. The cells, however, displayed receptor desensitization under the same conditions, that is, no response was observed upon repeated addition of the same agonist, EGF, insulin or IGF-I. Thus, the EGF receptor-initiated signalling was mediated by PtdIns 3-kinase associated with tyrosine-phosphorylated IRSs in short-term cultured rat hepatocytes.

Animals↗

Further evidence for the involvement of insulin receptor substrates in epidermal growth factor-induced activation of phosphatidylinositol 3-kinase.

In accordance with our recent results obtained with cultured rat hepatocytes [Fujioka, T. & Ui, M. (2001) Eur. J. Biochem. 268, 25-34], epidermal growth factor (EGF) gave rise to transient tyrosine phosphorylation of insulin receptor substrates (IRS-1 and IRS-2), thereby activating the bound phosphatidylinositol 3-kinase in human epidermoid carcinoma A431 cells normally abundant in EGF receptors (EGFR) and Chinese hamster ovary (CHO) cells transfected with full-length EGFR. These actions of EGF, although much smaller in magnitude than those of insulin or IGF-I in the same cells, were accompanied by tyrosine phosphorylation of EGFR rather than insulin or IGF-I receptors, never observed in wild-type CHO cells expressing no EGFR, and totally inhibited by an inhibitor of EGFR kinase, AG1478, that was without effect on insulin or IGF-I actions. Recombinant IRS-1 was phosphorylated on tyrosines upon incubation with purified EGFR from A431 cells and 32P-labeled ATP. When CHO cells were transfected with C-terminal truncated EGFR lacking three NPXY motifs responsible for direct binding to phosphotyrosine-binding domains of IRSs, no effect of EGF could be observed. We suggest that tyrosine phosphorylation of IRS-1 or IRS-2 could mediate EGFR-induced activation of phosphatidylinositol 3-kinase in mammalian cells.

Androstadienes↗