Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport

A wide variety of biological activities including the major metabolic actions of insulin is regulated by phosphatidylinositol (PI) 3-kinase. However, the downstream effectors of the various signaling pathways that emanate from PI 3-kinase remain unclear. Akt (protein kinase B), a serine-threonine kinase with a pleckstrin homology domain, is thought to be one such downstream effector. A mutant Akt (Akt-AA) in which the phosphorylation sites (Thr308 and Ser473) targeted by growth factors are replaced by alanine has now been shown to lack protein kinase activity and, when overexpressed in CHO cells or 3T3-L1 adipocytes with the use of an adenovirus vector, to inhibit insulin-induced activation of endogenous Akt. Akt-AA thus acts in a dominant negative manner in intact cells. Insulin-stimulated protein synthesis, which is sensitive to wortmannin, a pharmacological inhibitor of PI 3-kinase, was abolished by overexpression of Akt-AA without an effect on amino acid transport into the cells, suggesting that Akt is required for insulin-stimulated protein synthesis. Insulin activation of p70 S6 kinase was inhibited by approximately 75% in CHO cells and approximately 30% in 3T3-L1 adipocytes, whereas insulin-induced activation of endogenous Akt was inhibited by 80 to 95%, by expression of Akt-AA. Thus, Akt activity appears to be required, at least in part, for insulin stimulation of p70 S6 kinase. However, insulin-stimulated glucose uptake in both CHO cells and 3T3-L1 adipocytes was not affected by overexpression of Akt-AA, suggesting that Akt is not required for this effect of insulin. These data indicate that Akt acts as a downstream effector in some, but not all, of the signaling pathways downstream of PI 3-kinase.     

Bacillus cereus septicemia in a patient with severe aplastic anemia

A 78-year-old female was admitted with complaints of malaise and fatigue in the legs. The patient was diagnosed as severe aplastic anemia and treatment was started with metenolone and steroid pulse therapy. Administration of antibiotics and granulocyte-colony stimulating factor which led to a resolution of the high fever. About four months after admission, the patient developed vomiting and abdominal pain with a spiking fever. The next day after suddenly losing consciousness, she died. B. cereus was isolated from blood cultures. Autopsy specimens of the liver, cardiac muscle and lung showed changes due to B. cereus. This pathogen is widely distributed in nature. We should not overlook B. cereus as a contamination, but rather should consider it a potential pathogen in immunocompromised hosts, when it is isolated from blood cultures.     

Recent arguments in advanced gastric cancer treatment]

In advanced inoperable gastric cancer patients, survival was significantly prolonged for the group receiving antineoplastic treatment against only the best supportive care group by some randomized controlled studies. Greater prolongation of survival is expected from surgery in CR and PR cases because of the change from inoperable to operable. One problem is that the evaluation of response to the primary site is different between Japan and other countries. Outside of Japan, it is considered that barium contrast studies and routine endoscopy are not sufficient for tumor response assessment at the primary site. I think this is not true evaluation of the response to gastric cancer chemotherapy to exclude primary site assessment. We must generalize the Japanese criteria of gastric cancer chemotherapy throughout the world.     

A case of biliary cystadenoma with obstructive jaundice

Biliary cystadenoma is a rare cause of obstructive jaundice. We report a case of a 78-year-old Japanese man with biliary cystadenoma presenting repetitive abdominal pain and jaundice. Ultrasound sonography revealed a hyperechoic mass in the left lateral lobe of the liver. Histological examination revealed a biliary cystadenoma. Intracystic hemorrhage was assumed to be the cause of obstruction of the bile ducts.     

Modification of parallel activity elicited by propagating bursts in developing networks of rat cortical neurones

The fine specificity of the cellular immune response to Candida albicans (i.e., recognition of different antigenic components) between normal controls and human immunodeficiency virus-infected patients in various stages of disease was compared. C. albicans-specific T cells, enriched by antigen stimulation and interleukin-2 expansion, were challenged with antigenic fractions of different molecular weight obtained by SDS-gel fractionation of C. albicans extracts in the presence of autologous mononuclear cells as antigen-presenting cells. Proliferative responses showed similar patterns of reactivity between controls and category A and B seropositive subjects. Category C patients with concurrent C. albicans infections did not give rise to C. albicans-specific T cell lines, confirming the T cell defect. Patients without clinically evident C. albicans infection had a low but broad reactivity pattern of C. albicans-specific T cells. These results suggest that depletion of C. albicans-specific T cells, independent of their fine specificity, occurs along with disease progression.     

Design of multivariable feedback systems with infinite gain margin and decoupling

This letter discusses the problem of designing a feedback compensator that attains the infinite gain margin under the uncertainties of feedback gains. A sufficient condition is given for the existence of compensators and then it is shown that the condition becomes necessary subject to the requirement that the feedback system is decoupled. The nonlinear case is also discussed.     

Antitumor activity of degraded products of lentinan: its correlation with molecular weight

Twelve of 25 patients with mixed connective tissue disease complained of xerostomia and/or ocular symptoms of keratoconjunctivitis sicca. In addition to the clinical features of mixed connective tissue disease, all 12 patients had high titers of antibody to the ribonuclease-sensitive component of the extractable nuclear antigen. Eight patients had both clinical xerostomia and keratoconjunctivitis sicca, one had keratoconjunctivitis sicca and salivary gland enlargement, while there had xerostomia but no ocular complaints. Sj?rgren's syndrome was confirmed in all 12 patients by means of Schirmer's tests, Rose Bengal staining tests, salivary gland scintiscans, radionuclide excretion studies in saliva, parotid sialographies, and lip biopsies. At least three of these tests were abnormal in all patients.     

Dipolar-decoupled carbon-13 NMR study of highly oriented polyethylene films

Summary High-resolution solid-state ¹³C NMR spectra and ¹³C relaxation times T₁ and T₁ have been measured at 40–100° C for uniaxially oriented polyethylene films with the drawing direction parallel to the magnetic field; this sample has a unique morphological structure that the noncrystalline chains are nearly disordered irrespective of the high degree of drawing. A sharp resonance line(line A) appears at the position corresponding to the principal value ₃₃ of the chemical shift tensor for the CH₂ carbons with the trans-trans conformation. Another sharp linedine B) is observed at almost the same chemical shift as for the CH₂ carbons of polyethylene in solution. Although these observations are similar to those for a cold-drawn polyethylene sample reported previously, line B is much enhanced in intensity and the linewidth is narrower in the present sample, reflecting the disorientation of the noncrystalline component. It is found from T₁ measurements that line A contains two components with different molecular mobility, both being assigned to the crystalline components. On the other hand, the line B is composed of a single component assignable to the noncrystalline component with liquid-like molecular mobility.     

Design, fabrication, and evaluation of crystal-cored fibers for efficient second-harmonic generation based on Cerenkov-radiation-type phase matching

A formulation for calculating the optical second-harmonic power based on the Cerenkov-radiation-type phase matching is derived for a crystal-cored fiber. The prerequisite condition for high efficiency is expressed by a simple relation by use of the refractive indices of a core crystal, a core radius, and a fundamental wavelength. An organic crystal-cored fiber is designed and practically fabricated by the guiding principle derived here. A blue second-harmonic wave of 1.4 mW is obtained from a 1-mm-long fiber by use of a 60-mW semiconductor laser, and the second-harmonic intensity agrees well with the prediction. Degradation of the organic core crystal caused by the generated blue wave is observed, and the lifetime of the device is evaluated.