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Biomedical subjects

Y Aso

Publications and source records attributed to Y Aso.

At least 415 records · Page 23Linked to original sources

Study on the packing geometry, stoichiometry, and membrane interaction of three analogs related to a pore-forming small globular protein.

A de novo designed pore-forming small globular protein (SGP) with antitumor activity consists of four helices: 3 basic amphipathic helices composed of Leu and Lys surrounding a central hydrophobic helix composed of oligoalanine. These helices are connected by a beta-turn-forming sequence and two beta-turn-unfavorable ones (S. Lee, T. Kiyota, T. Kunitake, E. Matsumoto, S. Yamashita, K. Anzai, and G. Sugihara Biochemistry 1997, Vol. 36, pp. 3782-3791). In the present work, we designed and synthesized three new SGP analogs in order to study the stoichiometric packing geometry and stability of SGP. The replacement of alanines in the central helix of SGP with leucines (SGP-L), which make the helix much larger in size and more hydrophobic, resulted in an equilibrium of monomeric-trimeric structure. The replacement of some Lys residues by Glu residues in the hydrophilic regions of the amphipathic helices (SGP-E) led to a decrease in helical content and the formation of an equilibrium of monomeric-trimeric structure. The alteration of beta-turn regions with Gly residues, which makes these regions flexible (SGP-G), established an equilibrium of monomeric-dimeric states in buffer. The hydrophobic alpha-helix of SGP-L penetrated into the lipid bilayers in a manner that stabilized model membranes and biomembranes, whereas the central helices of SGP-G and -E destabilized them by forming channels. SGP and its analogs may be a useful model to study the role of the hydrophobic and hydrophilic regions in the formation of monomer-oligomer of proteins and to better understand the insertion of membrane targeting proteins into biomembranes.

Amino Acid Sequence↗

Small low-density lipoprotein and small low-density lipoprotein/total low-density lipoprotein are closely associated with intima-media thickness of the carotid artery in Type 2 diabetic patients.

BACKGROUND: The intima-media thickness (IMT) of the carotid artery, as determined by ultrasonography, is useful for reflecting the extent of subclinical atherosclerosis. We investigated the relationship between IMT and the serum concentrations of small low-density lipoprotein (LDL) in diabetic patients. METHODS: The study was conducted with 27 Type 2 diabetic patients (14 males and 13 females; mean age=62.6+/-8.3 years) and 12 age-matched healthy controls. The LDL subfraction was measured using a polyacrylamide gel electrophoresis method. Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) concentrations were measured by an enzyme immunoassay. The IMT was expressed as the maximum IMT (Max-IMT) and average IMT (Ave-IMT) of the carotid artery, measured by ultrasonography. RESULTS: Both the IMT and the small LDL concentrations were significantly increased in the diabetic patients compared with the healthy participants. The IMTs were significantly correlated with small LDL concentration and small LDL/total LDL more than LDL concentrations by multivariate analysis. The IMTs were not significantly correlated with the serum VEGF or PDGF concentrations. The patients with a larger IMT had a significantly higher prevalence of hypertension or ischemic heart disease than did the patients with a normal IMT. CONCLUSIONS: The increased small LDL concentrations and small LDL/total LDL, in addition to total LDL concentrations, in Type 2 diabetic patients are closely associated with increased IMT of the carotid artery.

Arteriosclerosis↗

Relationship between sympathetic skin response and power spectral analysis of heart rate variation in patients with type 2 diabetes.

We measured sympathetic skin response (SSR), a measure of sympathetic sudomotor function, and compared SSR with other quantitative neurological tests including power spectral analysis (PSA) of heart rate variations in 60 type 2 diabetic subjects. SSR was detected in all 20 age-matched healthy subjects but was absent in 17 patients with type 2 diabetes (28%) (P<.01). Even after exclusion of diabetic patients with absent SSR, the SSR amplitude in diabetic patients was significantly lower than in healthy subjects (P<.05). Both the low frequency power of R-R intervals, which reflects both cardiac sympathetic and parasympathetic function, and the postural fall in systolic blood pressure were significantly lower in the diabetic patients with absent SSR than in those with present SSR (P<.05 and.001, respectively). However, we found no significant difference in the high frequency power of R-R intervals, which reflects accurately cardiac parasympathetic function, between the diabetic patients with absent SSR and those with present SSR. In the diabetic patients with present SSR, SSR amplitude was also positively correlated with the postural fall in systolic blood pressure, low-frequency (LF) power, and high-frequency (HF) power. These results suggest that SSR is a useful and sensitive method for evaluating diabetic autonomic neuropathy, and that sympathetic sudomotor neuropathy may be preceded by cardiac parasympathetic neuropathy in patients with type 2 diabetes.

Diabetes Mellitus, Type 2↗

Clinical usefulness of doxazosin in patients with type 2 diabetes complicated by hypertension: effects on glucose and lipid metabolism.

This uncontrolled study investigated the effects of using the alpha 1-blocker doxazosin (2 mg or 4 mg daily for 3 months) to treat 21 hypertensive patients with type 2 diabetes, including eight obese individuals (body mass index [BMI] > or = 25.0 kg/m2). A significant reduction in systolic and diastolic blood pressure, beginning after 1 month of treatment, was seen. There was no significant change in BMI. Although there was no obvious improvement in glucose metabolism, doxazosin treatment noticeably reduced insulin resistance and significantly lowered triglyceride and free fatty acid levels. No significant changes were found in total cholesterol, high- or low-density lipoprotein-cholesterol, atherosclerotic index, or small or large subfractions of low-density lipoprotein-cholesterol. None of the patients showed any adverse effects. The beneficial effects of doxazosin on blood pressure and lipid and glucose metabolism shown in this study suggest that this drug is clinically useful as an anti-hypertensive agent for patients with diabetes.

Antihypertensive Agents↗

Assessment of peripheral neuropathy using measurement of the current perception threshold with the neurometer in patients with type 2 diabetes mellitus.

Measurement of current perception threshold (CPT) using the Neurometer at 2000, 250 and 5 Hz assesses function in three different nerve fibre types. This method was used to investigate peripheral neuropathy in 116 patients with type 2 diabetes mellitus and 38 healthy controls. The CPT at 2000 Hz was significantly higher in diabetic patients than in controls, and showed a significant negative correlation with motor and sensory nerve conduction velocities. At 250 Hz, CPT showed a significant positive correlation with the vibration perception threshold. At 5 Hz, the change in systolic blood pressure in the Schellong test in patients with hypoaesthesia tended to be less than in those with normal sensation or hyperaesthesia. Significantly higher CPT values were obtained in patients with proliferative diabetic retinopathy and macroalbuminuria. These data suggest that CPT is useful in detecting abnormalities of myelinated as opposed to unmyelinated nerve fibres in patients with type 2 diabetes.

Aged↗

The regularity of intersteroidal relations in urine as related to the law of mass action.

The relation between 14 urinary steroid excretions was investigated by intersteroidal regression analysis with urine from 59 follicular stage women, 135 luteal stage women and 5 female patients with adrenal disorders. The regularity of intersteroidal relation in urine, as detected for all steroid pairs of all groups studied, was explained in terms of the law of mass action, and a chemical equilibrium point was located with a high degree of reproducibility for each steroid and for each group. The theoretical and practical usefulness of urinary steroid regression analysis is emphasized in relation to the possible impact of multihormonal information on endocrinology.

Adrenal Gland Diseases↗