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Y Uehara

Publications and source records attributed to Y Uehara.

At least 91 records · Page 5Linked to original sources
PubMed1997

Chronic insulin hypoglycemia induces GLUT-3 protein in rat brain neurons.

Near-normalization of glycemia reduces the risks of chronic diabetic complications but increases the risk of serious hypoglycemia. Hypoglycemia can impair neuronal function in the brain and diminish awareness of subsequent hypoglycemic episodes, yet little is known about how neurons adapt to hypoglycemia. This study tests the hypothesis that isoform-specific alterations in brain glucose transport proteins occur in response to chronic hypoglycemia. To study this, groups of rats were injected with approximately 25 U/kg ultralente insulin daily at 1700 for 8 days to maintain hypoglycemia. Vascular-free and microvessel membrane fractions from brain were prepared for immunoblot analysis of GLUT-1 and GLUT-3 by use of isoform-specific antisera. Insulin treatment reduced blood glucose levels from 4.0 +/- 0.1 (vehicle-injected controls) to 1.7 +/- 0.1 mmol/l on day 8 (P < 0.001) and increased GLUT-3 protein expression (175.6% of control; P < 0.05). Microvascular GLUT-1 (55 kDa) tended to increase (195.6% of controls; P = 0.08) variably, whereas nonvascular GLUT-1 (45 kDa) was unchanged. We conclude that neuronal glucose transport protein (GLUT-3) expression adapts to chronic hypoglycemia. This adaptation may spare neuronal energy metabolism but could dampen neuronal signaling of glucose deprivation.

Animals↗
PubMed1997

Serum N-acetyl-beta-D-glucosaminidase activity in a genetic rat model of non-insulin-dependent diabetes mellitus.

Serum N-acetyl-beta-D-glucosaminidase activity (NAG) is a possible predictor of vascular injury in hypertension. We assessed whether the activity of this enzyme reflects vascular damage in a genetic rat model of non-insulin-dependent diabetes mellitus (NIDDM) in humans. Otsuka Long-Evans Tokushima Fatty (OLETF) rats fed a regular chow were treated with the angiotensin converting enzyme (ACE) inhibitor imidapril for 16 wk. Systolic blood pressure increased in a time-dependent manner in the untreated OLETF rats as compared with that in the control Long-Evans Tokushima (LET) rats. The blood pressure elevation was associated with increases in cardiac and aortic weight. Imidapril treatment significantly attenuated the blood pressure elevation and reduced the increases in cardiac and aortic weight. The untreated OLETF rats had higher plasma glucose and insulin concentrations than did the LET rats and presented with glucosuria at the age of 22 wk. Imidapril treatment strikingly decreased plasma glucose levels and the glucosuria. Plasma insulin concentrations decreased, approaching those of the non-diabetic control LET rats. ACE inhibitor treatment attenuated the nodular lesions in the glomeruli of OLETF rats and improved the kidney function. Serum NAG activity increased significantly by 35% in the untreated rats; this increase was attenuated significantly by imidapril treatment. The reduction in serum NAG activity correlated with improvement in cardiovascular injury. In contrast, there were no changes in urinary NAG excretion in the three OLETF rat groups. In addition, NAG excretion did not correlate with indices of cardiovascular injury. These data suggest that serum NAG activity is useful in predicting injury in the cardiovascular system in rats with diabetes mellitus.

Acetylglucosaminidase↗
PubMed1997

Immunosuppressant HR-325 attenuates progression of malignant arteritis in the kidney of Dahl salt-sensitive rats.

We investigated the effects of the immunosuppressant HR-325 on arterial lesions in Dahl rats with salt-induced hypertension. Forty-eight 6-wk-old Dahl salt-sensitive (DS) rats were divided into 1) a low-salt (0.3% NaCl) group, 2) a high-salt (4% NaCl) group, 3) a high-salt and low-dose (1 mg/kg) HR-325 group, and 4) a high-salt and high-dose (30 mg/kg) HR-325 group. The rats were treated for 8 wk. Various variables of renal function and morphological alterations in the kidney were assessed. Blood pressure was measured by the tail-cuff method. HR-325 significantly decreased systolic blood pressure in a dose-dependent manner throughout the study. HR-325 tended to decrease plasma creatinine level and increase creatinine clearance rate. Morphological studies revealed that HR-325 treatment strikingly resolved infiltration of immune-related cells in perivascular and intraluminal lesions, thereby decreasing the total arterial injury score by 32%. High-dose HR-325 also attenuated glomerulosclerosis and tubular injury by 35% and 34%, respectively, as compared with untreated high-salt Dahl S rats. Reduced levels of immune-related cells resulted in a decrease in urinary nitrite excretion. These data indicate that long-term treatment with the immunosuppressant HR-325 decreases systolic blood pressure in Dahl salt-sensitive rats, and that this decrease is associated particularly with resolution of infiltration of immune-related cells in arterial lesions. Hyperimmune state is responsible in part for the susceptibility of Dahl S rats to hypertensive organ damage.

Aniline Compounds↗
PubMed1997

Thymic nurse cells forming a dynamic microenvironment in spontaneous thymoma BUF/Mna rats.

Thymic nurse cells (TNCs) were studied using an animal model, BUF/Mna rats, which spontaneously develop benign thymomas of epithelial origin with age. The unusual increment and high availability of TNCs in this thymus enabled us to analyze TNCs directly either in tissue sections or on smears after enzymatic isolation. No structural or phenotypical abnormality in these TNCs was detected as assessed by electron microscopy and immunohistochemistry. Typical TNCs were widely distributed in the cortical areas but not in the medullary areas. They showed characteristic euchromatic bright nuclei and enclosed intra-TNC cells with an investment of relatively light cytoplasm with abundant small vesicles and rough-endoplasmic reticulum. The intra-TNC cells were mostly double positive (CD4+CD8+) cortical thymocytes, though macrophage populations could also be distinguished by their content of membrane-bounded phagosomes, multivesicular bodies and other inclusion bodies, and by their lack of cytoskeletal keratin filaments. High voltage electron microscopy revealed that intra-TNC cells were separated into several compartments by extremely thin internal veils of the TNC processes. The outer veils of the TNCs were continuous with occasional small gaps through which intra-TNC cells could migrate in and out of the compartments. Immunohistochemical analyses revealed that the TNCs per se were positive for MHC class I and class II, keratin and thymulin, but lacked both lymphocyte and macrophage markers. Among all adhesion molecules tested, ICAM-1 was strongly expressed on almost all TNCs. A minority of TNCs also contained either LFA-1 alpha or LFA-1 beta positive cells. These results suggest that TNCs may form a rather dynamic microenvironment for T cell development where either nursing or clearance of thymocytes take place, depending on the cellular components of intra-TNC cells. Macrophage populations may also play crucial roles as the third component within TNCs.

Age Factors↗
PubMed1997

Epalrestat, an aldose reductase inhibitor, improves an impaired generation of oxygen-derived free radicals by neutrophils from poorly controlled NIDDM patients.

OBJECTIVE: To study the in vivo effect of epalrestat (Epa), an aldose reductase inhibitor, on the generation of oxygen-derived free radicals by neutrophils from poorly controlled NIDDM patients (HbA1c > 10%). RESEARCH DESIGN AND METHODS: A total of 31 diabetic patients were randomly divided into two groups: an Epa(+) group of 16 patients treated with 150 mg/day epalrestat and an Epa(-) group of 15 patients treated without epalrestat. A control group of 20 age- and sex-matched normal healthy subjects also participated. HbA1c, postprandial plasma glucose (PPG), and neutrophil bactericidal function were measured before and at the end of the drug treatment period (4 weeks). Neutrophil bactericidal function was measured as chemilu-minescence amplified by a Cypridina luciferin analog (CLA), which is dependent on O2- generation, and by luminol (L), which is highly dependent on OCl- generation, in response to formyl-methonyl-leucyl-phenylalanine (fMLP). RESULTS: At the start of the experiment, both CLA-dependent chemiluminescence (CLA-DCL) and L-dependent chemiluminescence (L-DCL) were clearly decreased in diabetic subjects (64 and 54%, respectively; P < 0.05) compared with control subjects (2,182 +/- 144 and 3,221 +/- 173 kc.min-1.10(-6) cells, respectively). At the end of the experiment, CLA-DCL and L-DCL in the Epa(+) group were significantly improved by 44 and 46%, respectively; however, these values were still lower than the corresponding results in the control group. HbA1c and PPG in both the Epa(+) and Epa (-) groups were significantly higher than in the control group, and treatment had no effect on either HbA1c or PPG. CONCLUSIONS: These data suggest that epalrestat may be a useful drug to prevent infection by improving the impaired O2- and OCl- generation by neutrophils from poorly controlled NIDDM patients.

Aldehyde Reductase↗
PubMed1997

Lipid metabolism and renal protection by chronic cicletanine treatment in Dahl salt-sensitive rats with salt-induced hypertension.

We investigated the role of lipid metabolism in renal protection by chronic cicletanine treatment in Dahl salt-sensitive (Dahl S) rats with salt-induced hypertension. Forty-four 6-week old Dahl S rats were divided into four groups: (1) low-salt (0.3% NaCl) control group: (2) high-salt (4% NaCl) control group; (3) low-dose (10 mg/kg/day) cicletanine (CICL)-treated group given a high-salt diet; and (4) high-dose (30 mg/kg/day) cicletanine-treated group given a high-salt diet. The rats were treated for 6 weeks; blood pressure was measured by the tail-cuff method. Cicletanine significantly reduced the systolic blood pressure in a dose-dependent manner (223 mmHg in the high-salt controls vs 195 mmHg in the high-dose, high-salt group, p < 0.01). Cicletanine treatment did not affect plasma concentration of total cholesterol or triglyceride or free fatty acid; in contrast, it significantly decreased low-density lipoprotein (LDL) cholesterol and increased high-density lipoprotein (HDL) cholesterol. Morphological examination demonstrated that glomerulosclerosis in the kidney was significantly improved by 15% with high-dose cicletanine (p < 0.01). Multivariate analysis revealed that glomerular sclerosis was determined independently by LDL cholesterol levels and arterial injury score, but not by total cholesterol or HDL cholesterol levels or blood pressures. LDL cholesterol was also an independent predictor of urinary excretion of protein. Thus, it is suggested that cicletanine treatment lowers the levels of LDL cholesterol in Dahl salt-sensitive rats, and that besides blood pressure reduction, this decrease in LDL cholesterol level contributes, in part, to regression of glomerular injury in salt-induced hypertension.

Animals↗
PubMed1997

[Protein kinase inhibitors--screening of new molecular target therapeutics].

Protein kinases are critical enzymes in regulating cellular growth and differentiation. Protein tyrosine kinases are potential targets for new anti-cancer therapeutics because they are encoded by many oncogenes. We first identified herbimycin A as an inhibitor of Src tyrosine kinase by screening agents that cause morphological reversion of v-src oncogene transformed cells. We next developed a method for evaluating inhibitors of oncogenic signal transduction pathways based on different growth abilities between normal and transformed cells in a defined serum free medium and isolated new tyrosine kinase inhibitors angelmicins. Recently, we developed an assay system in which activities of protein kinase A, protein kinase C, protein tyrosine kinase and calmodulin-dependent protein kinase III were simultaneously detected on a single gel. This system should be useful for evaluating specificities and screening of protein kinase inhibitors.

3T3 Cells↗
PubMed1997

Long-term infusion of kallikrein attenuates renal injury in Dahl salt-sensitive rats.

We investigated whether long-term infusion of kallikrein would attenuate renal injury in salt-induced hypertension in Dahl salt-sensitive (Dahl S) rats. A subdepressor dose of purified rat urinary kallikrein (RUK) (700 ng/day) was infused intravenously by an osmotic minipump for 4 weeks in male Dahl S rats fed a high-salt (2% NaCl) diet. This dose did not affect the time-dependent elevation of blood pressure. However, urinary protein excretion was significantly decreased, and the glomerular filtration rate was increased. These beneficial effects were reflected morphologically by an attenuation of the glomerulosclerotic lesions and tubular injury seen in the hypertensive Dahl S rats. The kallikrein infusion increased the urinary excretion of bradykinin and stimulated the excretion of cyclic GMP, suggesting that the kallikrein-kinin-prostaglandin and nitric oxide axes were enhanced by the RUK infusion. The alterations induced by such infusion were potentiated by the concomitant administration of the angiotensin converting enzyme inhibitor alacepril. These studies indicated that long-term replacement with rat tissue kallikrein attenuates renal injury in hypertensive Dahl S rats, and this is probably mediated by an enhanced function of the kallikrein-kinin-prostaglandin and nitric oxide systems.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

The implication of renin-angiotensin system on renal injury seen in Dahl salt-sensitive rats.

Angiotensin II (Ang II) progresses to remodeling of the cardiovascular system through nonhemodynamic as well as hemodynamic effects. There have been few data in vivo on whether subpressor concentration of Ang II is exerted to injure directly the cardiovascular system in hypertension. To test this hypothesis, we investigated, using Dahl salt-sensitive (Dahl S) rats, whether subpressor dose of Ang II progresses to cardiovascular injury observed in salt-induced hypertension. Recent studies have provided evidence that renin-angiotensin inhibition protects against renovascular injury in human hypertension as well as in experimental animals. Particularly in the case of Dahl salt-sensitive rats, a genetic model of volume-dependent hypertension in humans, they are likely to develop more severe arterial and renal injuries than those seen in spontaneously hypertensive rats with similar blood pressure levels. The mechanism of the susceptibility to hypertensive injuries is uncertain; however, renin-angiotensin inhibition significantly improved morphologic and functional injuries in the kidney of Dahl S rats. Conversely, subpressor dose of Ang II infusion exacerbated renal function and progressed to glomerulosclerotic lesions. Alterations of Ang II concentration in physiologic range influenced morphologic and functional injuries in Dahl S rats. Multivariate analysis revealed that activity of the renin-angiotensin system is an independent risk factor to glomerular injury in salt-induced hypertension. These data are in favor of the therapeutic strategy in human hypertension that inhibition of renin-angiotensin system is of value to produce beneficial effects of blood pressure reduction on organ injuries.

Animals↗
PubMed1997

Differential localization of s and e antigens in hepatitis B virus-associated glomerulonephritis.

We report here a case of membranous glomerulonephritis associated with chronic hepatitis B (HB) virus infection and describe differential localization of HB antigens in glomeruli. The patient showed mild proteinuria and was positive for hepatitis B surface (HBs) antigen, hepatitis B envelope (HBe) antigen, and antibody to hepatitis B core (HBc) antigen in the serum. The antibody against hepatitis C was negative. A renal biopsy revealed membranous glomerulonephritis with mesangial proliferation. The immunohistochemical studies using monoclonal antibodies localized the HBe antigen along the capillary wall and the HBs antigen in the mesangial area. The immunoelectron microscopic study confirmed the localization of HB antigens: HBe antigen was located in the subepithelial and intramembranous electron dense deposits and HBs antigen in the mesangial deposits. Our present results provide the first report of the differential localization of HB antigens in glomeruli at both the light and electron microscopic levels. The differential localization of HB antigens will provide insight into the pathogenesis of membranous glomerulonephritis.

Adult↗
PubMed1997

[Non pharmacological therapy in hypertensive patients--effect of physical exercise on hypertension].

Many well-controlled studies have shown that non-pharmacological treatments are effective in lowering blood pressure, especially in mild hypertensive. The principle proven measures are (1) reductions of sodium intake, body weight (in obesity) and alcohol and (2) physical exercise. Physical exercise has been proven for the antihypertensive effectiveness last ten years. We have carried out mine studies and demonstrated the reduction of blood pressure by mild (approximately 50% of maximum oxygen uptake) intensity cycle ergo meter (60 min. x 3 times a week x 10 week) by -11/-6 mmhg. We found sympathicolytic action and plasma volume depletion for the depressor effects. In hypertensive patients, life style modifications including exercise are the first step in the treatments of mild hypertensives.

Alcohol Deterrents↗
PubMed1997

[Recent advances in development of antitumor tyrosine kinase inhibitors].

Protein tyrosine kinases are critical enzymes in regulating cellular growth and differentiation and are also deeply involved in oncogenesis since they are frequently activated in a variety of human cancers. Novel compounds that inhibit epidermal growth factor receptors (EGF-R) with high specificity and potency were developed, and their antitumor effects on EGF-R overexpressing cells and in vivo tumor models were demonstrated. Novel compounds that preferentially inhibit human glioma cells expressing truncated rather than wild-type EGF-R were also developed. Tyrphostin analogs which inhibit angiogenesis and thereby suppress tumor cell growth were also identified by screening inhibitors of Flk-1 tyrosine kinase.

Animals↗
PubMed1997

Role of Y chromosome of hypertensive parent in determination of blood pressure in normotensive offspring.

We investigated whether the sex of hypertensive parents mediates determination of blood pressure in their normotensive offspring. We analyzed medical checkup data from 7279 Japanese university students. Six hundred and forty-one students had one hypertensive parent with or without hypertensive grandparents, and 609 of these were available for the present analysis. Blood pressure levels in the students with one hypertensive parent were within the normotensive range; however, the blood pressure levels were higher than those in students without hypertensive relatives, and lower than those in students with two hypertensive parents. In the students with one hypertensive parent, systolic blood pressure levels were significantly higher in the male than in the female students. However, the sex of the hypertensive parent did not affect the blood pressure values of their offspring. Multivariate analyses revealed that body mass index was an independent predictor of systolic blood pressure solely in male students with a hypertensive father, but not in male students with a hypertensive mother. In female students with one hypertensive parent, body mass index was irrelevant to the determination of blood pressure. These findings suggest that different mechanisms determine blood pressure in the offspring of hypertensive parents, and that blood pressure determination mediated by body mass index in male students is linked to hypertensive Y chromosome.

Adolescent↗
PubMed1996

Inhibitors of anchorage-independent growth affect the growth of transformed cells on poly(2-hydroxyethyl methacrylate)-coated surfaces.

We have described a microplate colorimetric assay to quantitate anchorage-independent cell growth, using plates coated with an anti-adhesive polymer poly (2-hydroxyethyl methacrylate) (polyHEMA).We investigated whether this method could be applied to human cancer cells of epithelial origin. HAG-1, a non-tumorigenic human gall-bladder carcinoma cell line, and its pSVneo and c-H-ras transfectants, which are also non-tumorigenic, did not grow on a polyHEMA-surface. In contrast, the v-src transformant which produced tumors in nude mice and formed colonies in soft agar, was able to proliferate on the coated surface, suggesting that tumorigenicity of human cancer cells correlates with the ability to grow on a polyHEMA-coated surface. We report on the feasibility of this method as a screening system for inhibitors of oncogenic transformation. Herbimycin A and radicicol, which have been reported to block Src function, suppressed the growth of v-src-transformed NRK and HAG-1 cells on the non-adhesive polyHEMA-surface at concentrations significantly lower than on plastic. Differences in the inhibitory concentrations were not observed with KB cells, and cytotoxic agents such as adriamycin did not show any selectivity between the 2 surfaces. Growth of ras-transformed cells on the coated surface was selectively blocked by L-739,749, a farnesyltransferase inhibitor. The results demonstrate that compounds causing reversion of transformed cells to normal, hence, selectively inhibiting cell growth in anchorage-independent conditions, can be screened using this microtiter plate assay.

Adenocarcinoma↗
PubMed1996

A life stage of particle-laden rat dendritic cells in vivo: their terminal division, active phagocytosis, and translocation from the liver to the draining lymph.

Initiation of an adoptive immune response against pathogenic organisms, such as bacteria and fungi, may involve phagocytic activity of dendritic cells (DC) or their immature precursors as a prelude to antigen processing and presentation. After intravenous injection of rats with particulate matter, particle-laden cells were detected in the peripheral hepatic lymph. Since it has been known there is a constant efflux of DC from nonlymphoid organs into the draining peripheral lymph, we examined whether these particle-laden cells belonged to the DC or macrophage lineage. The majority of particle-laden cells in lymph showed immature monocyte-like cytology, and the amount of ingested particles was small relative to typical macrophages. We identified these particle-laden cells as DC based on a number of established criteria: (a) they had a phenotype characteristic of rat DC, that is, major histocompatibility complex class Ihigh+ and IIhigh+, intercellular adhesion molecule 1+ and 80% positive with the rat DC-specific mAb OX62; (b) they showed strong stimulating capacity in primary allogeneic mixed leukocyte reaction; (c) in vitro, they had little phagocytic activity; and (d) the kinetics of translocation was similar to that of lymph DC in that they migrated to the thymus-dependent area of the regional nodes. Furthermore, bromodeoxyuridine feeding studies revealed that most of the particle-laden DC were recently produced by the terminal division of precursor cells, at least 45% of them being <5.5 d old. The particle-laden DC, defined as OX62+ latex-laden cells, were first found in the sinusoidal area of the liver, in the liver perfusate, and in spleen cell suspensions, suggesting that the site of particle capture was mainly in the blood marginating pool. It is concluded that the particle-laden cells in the hepatic lymph are recently produced immature DC that manifest a temporary phagocytic activity for intravascular particles during or after the terminal division and that the phagocytic activity is downregulated at a migratory stage when they translocate from the sinusoidal area to the hepatic lymph.

Animals↗
PubMed1996

Contribution of sustained Ca2+ elevation for nitric oxide production in endothelial cells and subsequent modulation of Ca2+ transient in vascular smooth muscle cells in coculture.

To elucidate the intracellular Ca2+ (Ca2+i ) transient responsible for nitric oxide (NO) production in endothelial cells (ECs) and the subsequent Ca2+i reduction in vascular smooth muscle cells (VSMCs), we administrated four agonists with different Ca2+i-mobilizing mechanisms for both cells in iso- or coculture. We monitored the Ca2+i of both cells by two-dimensional fura-2 imaging, simultaneously measuring NO production as NO2-. The order of potency of the agonists in terms of the peak Ca2+i in ECs was bradykinin (100 nM) > ATP (10 microM) > ionomycin (50 nM) > thapsigargin (1 microM). In contrast, the order in reference to both the extent of Ca2+i reduction in cocultured VSMCs and the elevation in NO production over the level of basal release in ECs completely matched and was ranked as thapsigargin > ionomycin > ATP > bradykinin. Treatment by NG-monomethyl-L-arginine monoacetate but not indomethacin or glybenclamide restored the Ca2+i response in cocultured VSMCs to the isoculture level. In ECs, when the Ca2+ influx was blocked by Ni2+ or by chelating extracellular Ca2+, all four agonists markedly decreased NO production, the half decay time of the Ca2+i degenerating phase, and the area under the Ca2+i curve. The amount of produced NO hyperbolically correlated to the half decay time and the area under the Ca2+i curve but not to the Ca2+i peak level. Thus, the sustained elevation of Ca2+i in ECs, mainly a result of Ca2+ influx, determines the active NO production and subsequent Ca2+i reduction in adjacent VSMCs. Furthermore, L-arginine but not D-arginine or L-lysine at high dose (5 mM) without agonist enhanced the NO production, weakly reduced the Ca2+i in ECs, and markedly decreased the Ca2+i in VSMCs, demonstrating the autocrine and paracrine effects of NO (Shin, W. S., Sasaki, T., Kato, M., Hara, K., Seko, A., Yang, W. D., Shimamoto, N., Sugimoto, T., and Toyo-oka, T. (1992) J. Biol. Chem. 267, 20377-20382).

Animals↗
PubMed1996

Herbimycin A, a tyrosine kinase inhibitor, impairs hypercalcemia associated with a human squamous cancer producing interleukin-6 in nude mice.

Interleukin-6 (IL-6) is a multifunctional cytokine that is produced not only by a variety of normal cells but also by cancer cells. IL-6 produced by cancer cells stimulates the proliferation of these cancer cells in an autocrine/ paracrine manner and causes paraneoplastic syndromes including hypercalcemia, cachexia, and leukocytosis. We have reported previously that a human oral squamous cancer associated with hypercalcemia produces large amounts of IL-6, that animals bearing this cancer exhibit elevated levels of plasma IL-6, and that neutralizing antibodies to human IL-6 reverse hypercalcemia in tumor-bearing animals, indicating an important role of IL-6 in the hypercalcemia in this model. Because these cancer cells overexpress epidermal growth factor receptors (EGFR) with intrinsic tyrosine kinase (TK) activity similar to many other squamous cancers, we examined the effects of herbimycin A, a tyrosine kinase inhibitor, on IL-6 production and hypercalcemia in animals bearing this cancer to develop a new approach to treat the hypercalcemia associated with malignancy. Intraperitoneal administration (once a day for 2 days) of herbimycin A to cancer-bearing hypercalcemic mice reduced the plasma levels of human IL-6 and impaired the hypercalcemia. During 2-day treatment with herbimycin A, no changes were observed in tumor size. Of interest, plasma levels of mouse, but not human, soluble IL-6 receptors were also elevated. However, herbimycin A showed no effects on plasma levels of mouse soluble IL-6 receptors. Herbimycin A suppressed the tyrosine autophosphorylation of EGFR and IL-6 mRNA expression and production, all of which were stimulated by EGF. The data raise the possibility that TK inhibitors may be potential mechanism-based therapeutic agents for the treatment of hypercalcemia associated with squamous cancers which overexpress EGFR.

Animals↗