The purpose of this study was to investigate ocular blood flow hemodynamics in patients with diabetes mellitus. We used color Doppler sonography, in 22 normal subjects and 52 patients with (n = 25) or without (n = 27) diabetic retinopathy, to determine blood flow velocities and the resistive index of the central retinal artery. The resistive index of the central retinal artery in patients with diabetic retinopathy (0.85 +/‐ 0.09) was significantly greater (P < 0.01) than that in normal subjects (0.72 +/‐ 0.08) and in patients without diabetic retinopathy (0.81 +/‐ 0.09). The resistive index of the central retinal artery in the patients without diabetic retinopathy was also significantly greater than that of normal subjects (P < 0.01). The resistive index of ocular arterial flow was increased in the patients with diabetes mellitus and further increased in the presence of retinopathy. Increased resistance in the peripheral ocular vascular bed contributes to diabetic retinopathy, and this change is present before the appearance of overt diabetic retinopathy.

BackgroundInsomnia is associated with the onset and development of diabetes. Melatonin affects sleep quality and glucose metabolism in diabetic patients with insomnia. We administered ramelteon, an agonist of melatonin, to type 2 diabetic patients and investigated its effects on glucose metabolism and insomnia.MethodsThis multicenter, prospective, randomized, and observational pilot study was performed between April 2014 and April 2015 at three institutes in Japan. Patients were prescribed ramelteon 8 mg/day for 3 months (first period). And patients were divided at random into the continuation group that continued taking ramelteon and the discontinuation group that discontinued taking ramelteon for 3 additional months (second period). The primary endpoint was change in glycated hemoglobin (HbA1c) level. Secondary endpoints were changes in global Pittsburgh sleep questionnaire index (PSQI) score and other glucose metabolism makers.ResultsWe enrolled 42 patients, and 32 patients completed the first period. Their mean HbA1c was 6.7%, and global PSQI score was 8.1 on average. HbA1c level did not change but global PSQI score improved from 8.1 to 7.2 by ramelteon (P = 0.030). Thirty-one patients completed the second period. HbA1c level did not change in the continuation group, but it increased from 6.7% to 6.9% (P = 0.003) in the discontinuation group. Global PSQI score did not change in each group. There was no rebound insomnia.ConclusionTreatment with ramelteon did not change the HbA1c level but improved sleep quality in type 2 diabetic patients with insomnia. Discontinuation of ramelteon slightly increased the HbA1c level and did not worsen sleep quality.

A 44-year-old woman was admitted to our hospital with altered mental status and weakness in the left upper and lower limbs. A brain magnetic resonance imaging indicated multiple cerebral infarctions in the bilateral frontal and parietal lobes and in the left occipital lobe. Magnetic resonance angiography indicated overall arterial wall irregularity and stenosis. An electrocardiogram showed negative T waves, troponin I was elevated at 0.60 ng/mL, and an echocardiogram showed severe hypokinesis, leading to a diagnosis of ischemic heart disease; however, no stenosis was found at cardiac catheterization. No other etiology for the angiopathy could be found. Whole-body computed tomography demonstrated an adrenal tumor and urinary catecholamine levels were elevated. Following excision of the adrenal tumor, a diagnosis of pheochromocytoma was made. Postoperatively, the patient's arterial stenosis and cardiac abnormalities improved. It was hypothesized that the patient's cardiomyopathy and vasospasm were secondary to excessive catecholamine secretion from the pheochromocytoma.

To clarify the physiological roles of insulin receptor substrate‐1 (IRS‐1) in vivo, we made mice with a targeted disruption of the IRS‐1 gene locus. Mice homozygous for targeted disruption of the IRS‐1 gene were born alive but were retarded in embryonal and postnatal growth. They also had resistance to the glucose‐lowering effects of insulin, insulin‐like growth factor‐1 (IGF‐1) and factor‐2 (IGF‐2). These data suggest the existence of both IRS‐1‐dependent and IRS·1·independent pathways for signal transduction of insulin and IGFs. Moreover, we identified tyrosine phosphorylation of a 190‐kDa protein (pp190) as a novel substrate (IRS‐2) for insulin receptor kinase in livers of IRS‐1 deficient mice which can bind both P13‐kinase and Ash/Grb2.

U5 small nuclear RNA itself can act as a clastogenic and transforming agent when transfected into cells. In the previous work, the 3 half of the U5 small nuclear RNA first stem structure (designated RNA3S) was capable of driving normal cells into tumorigenic cells when expressed with a poly(A) tail (RNA3S ؉ ). This transformation critically depended upon the polypurine sequence GGAGAGGAA in RNA3S ؉ . In this work, we first examined the pre-␤-lactamase and luciferase (model secretory and nonsecretory proteins) translation with the in vitro synthesized RNA3S in rabbit reticulocyte lysate. The capped RNA3S with a poly(A) tail suppressed the translation. In addition, the polypurine sequence played a crucial role in affecting the secretory protein synthesis, indicating a primary action of RNA3S ؉ . Further studies revealed that the oligodeoxynucleotides, corresponding to the polypurine and its antisense sequences, directly contacted 28 S rRNA in ribosome and 7SL RNA in signal recognition particle, respectively, and differentially affected the nascent chain elongation of secretory protein synthesis. These results suggest that RNA3S؉ blocks a physiological regulatory function played by signal recognition particle and the ribosome in the secretory protein synthesis and support the idea that the transformation might result from a repressed cellular activity.Carcinogenesis proceeds through a series of genetic alterations involving oncogenes and tumor suppressor genes (1-3). It is also widely believed that carcinogenic initiation is caused by genetic mutation(s) induced by carcinogens. Initiated cells continue to exhibit various unusual phenomena leading to malignant neoplasia such as morphological transformation, immortalization (4), suppression of intercellular communication (5-7), loss of extracellular matrix protein (8, 9), and autonomous growth (10). However, the mechanisms underlying such uncertain alterations associated with all stages in carcinogenesis are still unknown.In our previous work based on the cell transformation induced by U5 small nuclear RNA (U5) (11), 1 the 3Ј half of the U5 first stem structure (12) (designated RNA3S) had an ability to convert normal rat fibroblastic 3Y1 cells to morphologically transformed cells at a marked frequency when expressed with a poly(A) tail as an RNA polymerase II-derived noncoding transcript (RNA3S ϩ ) (13). The morphologically transformed cells went on eventually to produce tumorigenic cells, suggesting that RNA3Sϩ is capable of driving the normal cells into the neoplastic stage. Additionally, RNA3Sϩ suppressed the fibronectin protein synthesis in HeLa cells, supporting the idea that it is indeed a new type of transforming agent. We thus call an RNA ϩ having a transforming activity such as RNA3S ϩ "transforming RNA." Based on these results, the transforming RNA might have the ability to perturb a regulatory system to maintain the normal cellular process. This transformation was critically dependent upon the polypurine sequence GGAGAG-GAA in RNA3S ϩ . Because the cells e...