The surface composition of asteroid 162173 Ryugu from Hayabusa2 near-infrared spectroscopy.

The near-Earth asteroid 162173 Ryugu, the target of the Hayabusa2 sample-return mission, is thought to be a primitive carbonaceous object. We report reflectance spectra of Ryugu's surface acquired with the Near-Infrared Spectrometer (NIRS3) on Hayabusa2, to provide direct measurements of the surface composition and geological context for the returned samples. A weak, narrow absorption feature centered at 2.72 micrometers was detected across the entire observed surface, indicating that hydroxyl (OH)-bearing minerals are ubiquitous there. The intensity of the OH feature and low albedo are similar to thermally and/or shock-metamorphosed carbonaceous chondrite meteorites. There are few variations in the OH-band position, which is consistent with Ryugu being a compositionally homogeneous rubble-pile object generated from impact fragments of an undifferentiated aqueously altered parent body.

Relationship of low-density lipoprotein particle size to plasma lipoproteins, obesity, and insulin resistance in Japanese men.

OBJECTIVE: To determine the clinical characteristics of patients with small low-density lipoprotein (LDL) particles among Japanese men with mild glucose intolerance and to investigate the relationship of LDL particle size to the levels of other plasma lipoproteins, obesity, insulin resistance, and blood pressure (BP). RESEARCH DESIGN AND METHODS: The subjects were 40 men with impaired glucose tolerance or diabetes treated by diet alone, and 40 healthy men matched for age and body mass index (BMI) were used as control subjects. LDL particle size was measured using gradient gel electrophoresis. RESULTS: Of the 40 patients with glucose intolerance, 19 had small LDL (particle size < 25.5 nm) compared with only 4 of the 40 control subjects. In the patients with small LDL, the plasma levels of cholesterol, triglycerides, and apolipoprotein B, the fasting serum immunoreactive insulin, and the waist-to-hip ratio were all higher than in the patients with normal LDL (particle size > or = 25.5 nm), while the high-density lipoprotein cholesterol level was lower. However, there were no significant differences in BMI, BP, or insulin sensitivity in a euglycemic clamp study between the small-LDL and normal-LDL subgroups. CONCLUSIONS: Japanese men with glucose intolerance frequently have small LDL, and this abnormality is associated with other dyslipoproteinemias and increased waist-to-hip ratio.

Structural properties of connectin studied by ultraviolet resonance Raman spectroscopy and infrared dichroism.

Ultraviolet resonance Raman spectra of solubilized connectin indicated the presence of beta-sheets and hydrogen-bonded irregular structures. Some Trp and Tyr sidechains are located in hydrophobic environments and some NHs of mainchain amides and Trp indoles are not easily reached by solvent water, suggesting the presence of folded structures constructed of the beta- and irregular parts. Infrared spectra showed an abundance of beta-sheets in a connectin fiber, some of which were aligned with their mainchain axes parallel to the fiber axis. Thus, the beta-spiral structure proposed for elastin is improbable in connectin. This conclusion is also supported by their different amide III frequencies in the visible Raman spectra. A possible filamentous structure of repeated domains, consisting of beta-sheets and irregular parts, is discussed.

Significance of angiotensin I-converting enzyme and angiotensin II type 1 receptor gene polymorphisms as risk factors for coronary heart disease.

The D allele of an insertion/deletion (I/D) polymorphism in the angiotensin I-converting enzyme (ACE) gene is associated with a risk of myocardial infarction, and the relative risk associated with the ACE D allele is increased by the C allele of an angiotensin II type 1 receptor (AT1R) gene polymorphism (an A-->C transversion at nucleotide position 1166) [28]. The relation of the ACE and AT1R gene polymorphisms to coronary heart disease and the severity of coronary artery stenosis has now been investigated in 133 patients with myocardial infarction (MI) or angina pectoris who underwent coronary angiography and in 258 control subjects. The frequency of the ACE DD genotype as compared with non-DD was significantly higher in the patients who experienced an MI and in the low-risk patients than that in the controls (P < 0.05). The DD genotype showed a significantly increased risk of MI (odds ratio 1.85). The frequency of the AT1R A/C genotypes did not differ between the patients and the controls. The severity of coronary stenosis in the patients was estimated by the number of affected vessels (> 75% stenosis) and the coronary score of Gensini. Neither the number of affected vessels nor the coronary score differed among the ACE I/D genotypes. However, the number of affected vessels was significantly greater in patients with the AT1R AC genotype than in those with the 4A genotype (1.93 +/- 0.27 vs. 1.27 +/- 0.99; P < 0.05) (CC genotype was not found in the patients). After excluding patients with diabetes mellitus, the coronary score of those with the AC genotype was also significantly higher than in those with the AA genotype (51.7 +/- 34.4 vs. 18.2 +/- 23.3; P < 0.01). These results suggest that the ACE D allele is associated with the occurrence of myocardial infarction, while the AT1R C allele is involved in the development of the coronary artery stenosis.

Binding of connectin to myosin filaments.

Binding of native connectin (2,100 kDa fragment of alpha-connectin) to myosin filaments was investigated using a sedimentation technique and densitometric estimations of the separated proteins. In the presence of 60 mM KCl and 5 mM phosphate buffer, pH 7.0, as much as 1.5 mol of connectin was bound to 1 mol of myosin, suggesting that some 150 connectin filaments bound to a single myosin filament of approximately 0.5 micron in length. This value was much more than the ratio found in muscle (12:1). It appeared that C protein did not affect the binding of connectin to myosin filaments.

Screening for variants of the uncoupling protein 2 gene in Japanese patients with non-insulin-dependent diabetes mellitus.

We examined genetic mutations in the coding regions of the uncoupling protein 2 (UCP2) gene in 100 patients with non-insulin-dependent diabetes mellitus (NIDDM). The sequences of each exon-intron boundary were detected by polymerase chain reaction (PCR) using specific primer pairs designed in the cDNA sequence of UCP2 and a cycle-sequence method. Using the specific primer pairs in the intron 5'- or 3'-untranslated region, each exon with its exon-intron boundaries was amplified with the PCR method, and the PCR products were analyzed using a single-strand conformation polymorphism (SSCP) method. One nucleotide substitution in exon 4 was found, which exchanged Ala (gcc) at position 55 of the amino acid sequence for Val (gtc), previously reported in Denmark by Urhammer et al in 1997. The polymorphism was reanalyzed in all patients and 120 normal subjects using a PCR-restriction fragment length polymorphism method. There was no difference in the genotype distribution between patients and normal subjects, and our genotype distribution was similar to the Danish study. Furthermore, there were no clinical differences between genotype groups among the patients. No other mutation including the exon-intron boundary was found in these patients. Genetic mutations of UCP2 may not be commonly associated with obesity or diabetes in Japanese subjects.

Serum paraoxonase activity and its relationship to diabetic complications in patients with non-insulin-dependent diabetes mellitus.

Paraoxonase (PON) is an esterase associated with high-density lipoprotein (HDL). Serum PON activity is affected by PON gene polymorphism (L/M, Leu-Met54, and Q/R, Gln-Arg191). We investigated PON activity and polymorphism in 108 patients (53 men and 55 women) with non-insulin-dependent diabetes mellitus (NIDDM) and 161 control subjects (82 men and 79 women) matched to the patients by age and gender. Serum PON activity was determined using paraoxon as a substrate. PON gene polymorphisms were detected by the restriction fragment length polymorphism method after a polymerase chain reaction. The mean PON activity in the patients was significantly lower than in the controls (116+/-55 and 162+/-57 U/L, respectively, P < .001). The distribution of each genotype showed no difference between the patient and control groups, and PON activity increased in the order of the QQ < OR < RR genotype and MM < LM < LL genotype in both groups. However, among each genotype subgroup, the activity was lower in patients than in controls. Forty-one patients with retinopathy had lower PON activity than those without the complication (94+/-36 and 129+/-61 U/L, respectively, P < .002). There was also a significant difference in PON activity between patients with and without overt proteinuria (93+/-38 and 122+/-58 U/L, respectively, P < .05). Logistic analysis showed that serum PON activity was one of the significant factors for retinopathy. These results suggest that decreased PON activity in patients with NIDDM is involved in diabetic vascular complications.

Systemic lupus erythematosus relapse with lupus cystitis.

A 45-year-old woman who had been diagnosed as having systemic lupus erythematosus (SLE) at the age of 28 years and who had been in remission developed severe urinary frequency, watery diarrhea, vomiting and weight loss. She also developed acute renal failure and her serological examination was consistent with active SLE. She had a markedly decreased urinary bladder capacity of 20 ml with hydroureteronephrosis. Histopathological study of her urinary bladder biopsy specimen showed mucosal edema, infiltration by lymphocytes and granulocytes, and deposition of IgA in the epithelium and submucosal region. We diagnosed this as a case of lupus cystitis. The patient's symptoms were alleviated by bilateral nephrostomy and corticosteroid therapy. In the present episode the patient showed none of the usual symptoms of SLE. This case and others reported in the literature show that lupus cystitis presents with specific signs and symptoms and therefore, this syndrome may represent a specific clinical manifestation of SLE.

Paraoxonase gene polymorphism in Japanese subjects with coronary heart disease.

We investigated the association of paraoxonase (PON) gene polymorphism with both the occurrence of coronary heart disease (CHD) and the severity of coronary artery stenosis in Japanese subjects. PON is a protein associated with plasma HDL. It has been hypothesized an A/B (Gln 192-->Arg) polymorphism of PON may be involved in the pathogenesis of CHD, especially among subjects with non-insulin-dependent diabetes mellitus (NIDDM). The polymorphism was determined in 134 patients with myocardial infarction (MI) or angina pectoris, and in 252 healthy subjects as controls. The frequencies of the AA, AB, and BB genotypes in the patients were 15, 50 and 35%, respectively, and these frequencies did not differ from those in control subjects (14, 49, and 37%). The relative risk of CHD was not found to be associated with these genotypes. These data also were similar among selected subgroups (patients with MIs, those with a low-risk lipoprotein profile for CHD, and those with NIDDM). Neither the number of affected vessels nor Gensini's scores differed among the genotype groups. Our case-control study in Japanese subjects did not show that the PON A/B polymorphism is associated with a risk of CHD.

Neuropeptide Y Y1 receptor polymorphism as a prognostic predictor in Japanese patients with IgA nephropathy.

BACKGROUND: Neuropeptide Y exhibits a vasoconstricting action and regulates systemic blood pressure as well as noradrenalin. There are 5 types of NPY receptors, Y1 - Y5, which were introduced by pharmacological differences. Recently, a single point mutation in the first intron of the NPY Y1 receptor (NPYY1R) was reported. SUBJECTS AND METHODS: In this study, we investigated the relationship between NPYY1R gene polymorphism and clinical characteristics in patients with IgA nephropathy using polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Distribution of the NPYY1R genotypes which were defined as YY, Yy and yy genotypes, did not differ between 60 normal control subjects and 68 patients with IgA nephropathy (15 : 36 : 9 versus 21 : 40 : 7, respectively). In IgA nephropathy patients, the incidence of hypertension and the rate of urinary protein excretion were slightly higher in the non-YY genotype than in the YY genotype group (23% versus 5% and 1.1 +/- 1.2 versus 0.6 +/- 0.4 g/24 h, p = 0.09 and p = 0.05, respectively). The reciprocal of the serum creatinine level was estimated to determine the deterioration in renal function during follow-up after the renal biopsy. The level was lower in the non-YY genotype than in the YY genotype group (-0.002 +/- 0.064 vs 0.033 +/- 0.053/month, respectively, p < 0.01). Multiple regression analysis for the reciprocal of the serum creatinine level revealed that the NPYY1R genotype was an effective variable (p < 0.01). CONCLUSION: In conclusion, we propose that the NPYY1R gene polymorphism may be a novel prognostic predictor in patients with IgA nephropathy.

Effect of a polymorphism of endothelial nitric oxide synthase gene in Japanese patients with IgA nephropathy.

BACKGROUND: Nitric oxide (NO) is synthesized by endothelial cell NO synthase (ecNOS) on vascular endothelium, and it plays a key role in the regulation of blood flow and pressure. A polymorphism of the ecNOS gene was recently shown to be associated with the development of cardiovascular disease. PATIENTS AND METHODS: We investigated the ecNOS gene polymorphism in 68 Japanese patients with IgA nephropathy (IgAN) and 134 normal controls. RESULTS: The genotype distributions were not different between the normal controls and the IgAN patients (ecNOS4b/b: ecNOS4b/a: ecNOS4a/a = 106:27:1 and 50:18:0, respectively). There was no significant difference in the renal histopathological grading between the patients with ecNOS4b/a and ecNOS4b/b. However, among the subgroup of patients whose duration of illness was two or more years, the advanced histopathological grading was more frequent in the patients with the ecNOS4b/a genotype (than in those with the ecNOS4b/b (p = 0.04)). The incidence of hypertension was also higher in the patients with the ecNOS4b/a genotype (50% in ecNOS4b/a versus 12% in ecNOS4b/b, p = 0.04). CONCLUSION: These results suggest that the ecNOS4b/a genotype (or ecNOS4a allele) of the ecNOS gene polymorphism may be involved in the progression of IgAN.

Hypothyroidism preceding hyperthyroidism in a patient with continuously positive thyroid stimulating antibody.

A 62-year-old woman was initially hypothyroid and then developed hyperthyroidism with continuously positive thyroid-stimulating antibody (TSAb). When she visited our hospital with the complaint of the feel of skipping beats, her serum free T4 level was initially low and thyrotropin (TSH) level was slightly elevated. One month after starting the supplement therapy with l-T4, she developed hyperthyroidism with increased 123I-thyroid uptake. TSH-binding inhibitor immunoglobulin (TBII) was slightly elevated only during the hypothyroid stage. Throughout the whole course, TSAb was continuously positive, while thyroid stimulation-blocking antibody (TSBAb) was not detectable. Primary hypothyroidism with TSAb may suggest the possibility of subsequent development of hyperthyroidism.

Trp64Arg mutation of beta 3-adrenergic receptor and insulin sensitivity in subjects with glucose intolerance.

We investigated the relationship between the Trp64Arg mutation in the beta 3-adrenergic receptor gene and insulin sensitivity, which was evaluated by the euglycemic-hyperinsulinemic-clamp technique, in 54 patients with impaired glucose tolerance (IGT) or non-insulin dependent diabetes mellitus (NIDDM) who were not receiving insulin therapy. The frequencies of Trp/Trp, Trp/Arg, and Arg/Arg genotypes in the patients were 63.0, 33.3, and 3.7%, respectively, which did not differ significantly from those of the 227 controls (67.0, 33.3, and 3.7%, respectively, which did not differ significantly from those of the 227 controls (67.0, 31.3, and 1.8%, respectively). The mean glucose infusion rate of the 34 patients with Trp/Trp did not differ from that of the 18 patients with Trp/Arg (4.3 +/- 2.2 and 5.3 +/- 2.4 mg/kg/min, respectively); while that of the 2 patients with Arg/Arg was 11.5 mg/kg/min. There were no differences in the BMI or fat distribution in the abdomen between each genotype of patients, although the frequency of the Arg64 allele tended to increase with body mass index (BMI) in the control subjects under 60 years of age, which suggests that the mutation is involved in weight gain.

Localized polyarteritis nodosa in the forearm and epididymis.

We report localized polyarteritis nodosa in a 31-year-old man who had painful nodules in the left forearm and scrotum. Histopathological findings of both tissues revealed distinct arteritis. However, he had no clinical evidence of any systemic disease. We finally diagnosed this case as a localized polyarteritis nodosa occurring in both the left forearm and epididymis. This form of polyarteritis nodosa has not been reported in the literature.

Simple obesity with cardiomyopathy of obesity.

A 32-year-old obese female was hospitalized with dyspnea. Echocardiogram revealed left ventricular dilatation. Chest X-ray film showed enlarged heart size and prominent pulmonary congestion. Simple obesity with congestive heart failure (CHF) due to cardiomyopathy of obesity was diagnosed according to the absence of obvious disease that caused obesity or CHF. After diet therapy and medication, subjective symptoms disappeared and body weight was reduced from 137 kg to 85 kg. Although few reports of cardiomyopathy of obesity have been reported in Japan, we propose the possibility that similar cases will be on the increase because Japanese dietary habits are now becoming more similar to those of Caucasians.

[Preclinical and clinical studies on the efficacy of bifonazole in patients with tinea pedis at 10 years after approval. Part 1. Susceptibility to bifonazole of clinical isolates of dermatophytes].

An investigation was carried out to determine whether or not here had been any changes in the susceptibility of clinically isolated strains of Trichophyton metagrophytes and Trichophyton rubrum (both leading causes of tinea) to bifonazole, an imidazole derivative and antifungal for topical use. Susceptibility was measured in 107 strains of these fungi isolated from clinical samples during a study on the treatment of tinea pedis with Mycospor cream in 1995, 42 strains isolated and stored in 1990, and 39 strains isolated and stored prior to development of the drug. The results are as follows: (1) There was no distinct difference in the susceptibility to bifonazole of T. mentagrophytes strains isolated before 1986 and those isolated in 1990 or 1995. (2) T. rubrum strains isolated before 1986 were slightly more susceptible to bifonazole than those isolated in 1995, while the 1990 strains were slightly less susceptible than the 1995 strains, but the difference was not significant. (3) The highest MICs of bifonazole for all the T. mentagrophytes and T. rubrum strains isolated from before 1986 and those in 1995 were relatively low, being 2.5 micrograms/ml and 1.25 micrograms/ml, respectively. These results suggest that no resistance or reduced susceptibility to bifonazole has emerged among clinical isolates of dermatophytes since the development of the drug.

[Fundamental and clinical studies on the efficacy of bifonazole in patients with tinea pedis at 10 years after approval. Part 2. Clinical evaluation].

The usefulness of bifonazole (Mycospor), a topical imidazole antifungal agent approved 10 years ago, was evaluated for the treatment of tinea pedis. Mycospor cream was applied by 141 patients with tinea pedis once daily for 4 233ks, and the clinical efficacy and adverse reactions (as well as any correlations with susceptibility of isolates and the mycological activity of the agent against these isolates) were studied. The results were then compared to those of a previous study. The following results were obtained. 1. Mycological activity Mycological examination results became negative in 63.2% (36/57) of the patients with plantar tinea pedis, in 94.1% (32/34) of those with interdigital tinea pedis, and in 74.7% (68/91) of all tinea pedis patients. 2. Mycological activity and MIC No correlation was found between the MICs of bifonazole against the pathogenic fungi and the rate of eradication on mycological examination. 3. Improvement of symptoms The improvement rates for local symptoms were 82.5% for plantar tinea pedis, 85.7% for interdigital tinea pedis, and 83.7% for all tinea pedis. 4. Clinical efficacy Good clinical efficacies were found in 61.4% of the patients with plantar tinea pedis, in 88.6% of those with interdigital tinea pedis, and in 71.7% of all patients. 5. Safety Regarding adverse reactions, what seemed to be contact dermatitis was reported in 5 out of 127 cases (3.9%). The reaction decreased or disappeared in all cases. 6. Usefulness Mycospor was found to be useful in 64.9% of patients with plantar tinea pedis, in 88.6% of those with interdigital tinea pedis, and in 73.9% of all tinea pedis patients. 7. Comparison with former results The results obtained in the present clinical study were comparable to those obtained in patients with tinea pedis treated in a double-blind comparative study conducted during the development of as a new topical antifungal agent. From the above results, Mycospor cream was confirmed to be still useful, although it has been used widely for the topical treatment of cutaneous mycoses in the past 10 years since its approval.

Henoch-Schönlein purpura with rapidly progressive glomerulonephritis and fatal intraperitoneal hemorrhage in an adult.

We report here the autopsy findings in a 51-year-old man who had been admitted with Henoch-Schönlein purpura (HSP) accompanied by rapidly progressive glomerulonephritis and massive intraperitoneal hemorrhage, leading to death. While the intraperitoneal hemorrhage was the primary cause of death, the patient may have suffered widespread intraperitoneal vasculitis due to HSP, or hemorrhagic pancreatitis due to the concurrent administration of a steroid and furosemide. We emphasize the acute hemorrhagic pancreatitis is a possible complication in patients with generalized vasculitis, including HSP and collagen disease, during the concurrent administration of steroids and other agents.

Autophosphorylation of beta-connectin (titin 2) in vitro.

Phosphorylation of beta-connectin (titin 2), an elastic protein of chicken breast muscle, occurred in the presence of [gamma-32P] ATP, 0.2 mM CaCl2 and 25 mM phosphate buffer, pH 7.0. Addition of 3 mM MgCl2 did not affect the phosphorylation. However, Ca2+ ions were required for the phosphorylation and EGTA inhibited it even if MgCl2 were present. Myosin light chain kinase (gizzard MLCK), cAMP dependent protein kinase (A kinase), and protein kinase C (C kinase) did not phosphorylate beta-connectin in vitro under optimal conditions. Thus it appears that beta-connectin, possibly containing a domain homologous with MLCK, has an autophosphorylating action.