Yasuhiro Ohno

Comprehensive study of urinary cortisol metabolites in hyperthyroid and hypothyroid patients.

Objective  To further analyse the significance and mutual relationship of thyroid function‐linked alterations in cortisol metabolism that have been separately and variously reported.

Clinical and genetic characteristics of patients with autoimmune thyroid disease with anti-islet autoimmunity

In contrast to the large number of studies on autoimmunity against the thyroid gland in patients with type 1 diabetes mellitus, little is known about the anti-islet autoimmune status in patients with autoimmune thyroid diseases (AITDs). We therefore studied the anti-islet autoimmune status in patients with AITD and the clinical and genetic characteristics of AITD patients with anti-islet autoimmunity. The positivity and titer of glutamic acid decarboxylase antibody (GAD Ab) were studied in 866 Japanese patients with AITD (546 with Graves disease and 320 with Hashimoto thyroiditis), 221 patients with thyroid disease of nonautoimmune origin, and 282 control subjects. The clinical characteristics and genotypes of HLA-DRB1, DQB1, and CTLA4 were compared between AITD patients with and without GAD Ab. The prevalence of GAD Ab was significantly higher in AITD patients than in control subjects (5.8% vs 2.1%, P = .01), particularly in Graves disease (7.1% vs 2.1%, P = .0019). The prevalence of diabetes mellitus was significantly higher in AITD patients with GAD Ab than in those without (40.0% vs 10.1%, P < .0001), particularly in those with a high titer of GAD Ab (high vs low titer: 64% vs 16%, P = .001) and also in those positive for insulinoma-associated antigen 2 (IA-2) Ab (IA-2 positive vs negative: 75.0% vs 31.3%, P = .016). The AITD patients with GAD Ab were characterized by younger age at onset of diabetes, lower body mass index, higher hemoglobin A(1c) level, and higher frequency of insulin therapy than those without GAD Ab. The frequency of the DRB1*0405-DQB1*0401 haplotype was significantly higher in AITD patients with GAD Ab than in those without GAD Ab and control subjects. A single nucleotide polymorphism (rs3087243) of CTLA4 was significantly associated with AITD, but not with positivity of GAD Ab. These results indicate that patients with AITD, and in particular Graves disease, are prone to develop β-cell autoimmunity and insulin-requiring diabetes, particularly those with a high titer of GAD Ab and/or positive for both GAD and IA-2 Ab. Glutamic acid decarboxylase Ab positivity in AITD patients was associated with HLA, conferring susceptibility to type 1 diabetes mellitus.

A novel copper(I) cluster stabilized by a dithiolate ligand having a conjugated TTF moiety

Abstract A copper(I) complex of a dithiolate ligand which is a TTF derivative has been synthesized and characterized. The structure of this complex, [Me4N]2[Cu4(C8H6S8)3]·Me2CO, is shown to be the first example of a metal cluster coordinated with a new TTF-fused dithiolate ligand. The complex is easily oxidized and shows radical properties.

Efficacy and safety of metformin for treatment of type 2 diabetes in elderly Japanese patients.

Aim:  The maximum dosage of metformin allowed for clinical use in Japan is much less than half that in Western countries, making it difficult to apply the results of clinical trials in Western countries to Japanese patients. In particular, the efficacy and safety of metformin in elderly patients are largely unknown.

Indomethacin augments inhibitory effects of interferons on lymphoproliferative response

Lectin-induced lymphoproliferative response was enhanced by the addition of indomethacin to the culture and in contrast, suppressed by the addition of interferon. However, when indomethacin and interferon were concomitantly present in the lectin-driven cultures, the suppressive effect of interferon on the lymphocyte blastogenesis surpassed the enhancing effect of indomethacin on the response. Furthermore, and unexpectedly, the inhibitory effect on the response due to interferon was definitely augmented in the presence of indomethacin as compared with the response in the absence of indomethacin.

Gamma interferon enhances mitogenic responses induced by pokeweed mitogen

Interferon (IFN)-induced suppression of the lectin-stimulated lymphoproliferative response was studied comparatively with human IFN-alpha, IFN-beta and IFN-gamma, using an equal unit of their antiviral activity ranging from 31.25 to 1000 IU/ml. Both IFN-alpha and IFN-beta inhibited phytohemagglutinin (PHA) and pokeweed mitogen (PWM)-stimulated lymphoblastogenic response similarly in a dose-related fashion, but the IFN-gamma effect was far less. Indeed, the PWM-stimulated lymphocyte blastogenesis in the cultures incubated for 7 days was enhanced in the presence of IFN-gamma at a concentration of 62.5 IU/ml. The enhancing effect was found to be highest at the lowest concentration of IFN-gamma examined. The IFN-gamma induced enhancement of lectin-stimulated blastogenesis was found mainly in the PWM cultures incubated for 7 days but less in cultures incubated for 5 days or in PHA cultures incubated for 3 days, suggesting that the observed effect might be caused by the activation of interleukin production.

EPIDEMIOLOGICAL INVESTIGATION OF INSULIN RESISTANCE SYNDROME (SYNDROME X) IN A CITY IN JAPAN

1. In order to study the prevalence of insulin resistance syndrome (syndrome X) in Japanese subjects, inhabitants aged above 40 years living in Osaka‐Sayama city from September 1992 through December 1993 were investigated. The population‐based study was performed on 2498 subjects (661 males and 1837 females) constituting 10.9% of the total population aged above 40 years.

Anti-albuminuric effect of losartan versus amlodipine in hypertensive Japanese patients with type 2 diabetes mellitus: A prospective, open-label, randomized, comparative study

UNLABELLED Abstract. BACKGROUND The antiproteinuric effect of the angiotensin II receptor-antagonist losartan has been observed in patients with type 2 diabetes mellitus (T2DM). Proteinuria is considered to be a predictor of the progression of kidney disease. OBJECTIVE The aims of the present study were to compare and examine the ability of losartan and amlodipine to ameliorate albuminuria in hypertensive Japanese patients (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) with T2DM and whether the change in albuminuria was associated with a change in glomerular filtration rate (GFR). METHODS This prospective, open-label, randomized, comparative study was conducted over 3 months at the Kinki University School of Medicine, Osaka-Sayama, Japan. Hypertensive patients with T2DM were enrolled and randomly assigned to 1 of 2 study groups receiving either losartan (25-100 mg/d) or the calcium channel-blocker amlodipine (2.5-5 mg/d). Urinary albumin excretion (UAE), creatinine clearance, and GFR were recorded at study initiation (baseline) and study end (month 3). The GFR was measured from the fractional renal accumulation of (99m)Tc-diethylenetriaminepentaacetic acid. Adverse events (AEs) were monitored by a clinical research nurse during the examination. RESULTS Fifty patients were asked to enroll and 38 returned the informed written consent. Thirty-five Japanese patients were included in the final study analysis. Seventeen patients were assigned to the losartan group (male sex, 10 [58.8%]; mean [SD] age, 58.1 [8.2] years) and 18 were assigned to the amlodipine group (male sex, 10 [55.6%]; mean [SD] age, 57.4 [8.9] years); no significant between-group difference in demographics was observed. A significant decrease from baseline to month 3 of mean (SD) UAE was observed in the losartan group (352.5 [556.6] mg/d vs 275.7 [466.1] mg/d; P = 0.048). No significant difference in mean (SD) UAE was observed in the amlodipine group for the same time period (298.2 [416.6] mg/d vs 322.7 [415.4] mg/d). There was a statistically significant difference found in the mean (SD) percent change of UAE from baseline to month 3 in the losartan group compared with the amlodipine group (-23.52 [28.42] vs +27.90 [63.51]; P = 0.004). Neither group was associated with a significant change in GFR during the course of the study. No patient discontinued the study due to AEs that were considered, by the investigator, to be possibly or probably associated with study treatment. CONCLUSIONS Treatment with losartan, but not amlodipine, was associated with a reduction in albuminuria in these hypertensive Japanese patients with T2DM within a period as short as 3 months. Neither drug was associated with a significant change in GFR. Therefore, the reduction of UAE was independent of a change in the GFR.

S · · · S Contact-assembled silver( I ) complexes of 4,5-ethylenedithio-1,3-dithiole-2-thione having unique supramolecular networks

Two silver(I) complexes of 4,5-ethylenedithio-1,3-dithiole-2-thione (C 5 H 4 S 5 ), [{Ag(C 5 H 4 S 5 ) 3 } ClO 4 ·CH 3 CN] 2 and [Ag(C 5 H 4 S 5 )CF 3 SO 3 ] ∞ have been synthesized and characterized crystallographically. They have unique dimeric and two-dimensional structures respectively and are assembled by S · · · S contacts. The finding of the shortest S · · · S contacts (3.284 and 3.262 A) in these complexes indicated that the co-ordination linkage in metal complexes containing these types of sulfur donor compounds could be expected to control the intra- or inter-molecular interactions. The co-ordination mode of the C 5 H 4 S 5 ligand has also been discussed.