Synthesis of six-membered silacycles by borane-catalyzed double sila-Friedel-Crafts reaction.

We have developed a catalytic synthetic method to prepare phenoxasilins. A borane-catalyzed double sila-Friedel-Crafts reaction between amino group-containing diaryl ethers and dihydrosilanes can be used to prepare a variety of phenoxasilin derivatives in good to excellent yields. The optimized reaction conditions were also applicable for diaryl thioethers to afford their corresponding six-membered silacyclic products. The gram-scale synthesis of a representative bis(dimethylamino)phenoxasilin and the transformation of its amino groups have also been demonstrated.

Relationship between the lifestyle of a Siboglinid (Pogonophoran) polychaete, Oligobrachia mashikoi, and the total sulfide and nitrogen levels in its habitat.

A gutless polychaete of the family Siboglinidae, Oligobrachia mashikoi, known in the past as a beard worm of the group Pogonophora, inhabits Tsukumo Bay of the Noto Peninsula in the Sea of Japan. Photographs were taken of this polychaete projecting about one third of the length of its tentacles outside of its tube. The tube protruded several mm from the sea bottom. These are the first field photographs of beard worms. The trophosome of this beard worm harbors sulfur-oxidizing bacteria. In fact, the muddy sediment where this worm inhabits smells slightly of hydrogen sulfide. Total sulfide levels, which can be an indicator of the generation of hydrogen sulfide gas, were measured at 10 locations in the bay. Furthermore, at the location which this species inhabits, the total sulfide levels in the vertical direction were determined. In addition, the total nitrogen levels, which can indicate the quantity of organic substances, were measured. The sediment inhabited by this worm was determined to have total sulfide levels of 0.24-0.39 mg/g dry mud, measured in the form of acid-volatile sulfide-sulfur. The total nitrogen levels were 1.0-1.5 microg/mg dry mud. These values suggest that the bottom of Tsukumo Bay has not been deteriorated by eutrophication. The levels were, however, highest in the surface layer of the sediment. These results suggest that hydrogen sulfide is generated in the surface of the sediment by sulfate-reducing bacteria, and that O. mashikoi appears to able to live in an environment that contains a slight amount of sulfide.

Colonoscopic classification of internal hemorrhoids: usefulness in endoscopic band ligation.

BACKGROUND: Bleeding is one of the main symptoms of internal hemorrhoids. However, the conventional Goligher's classification of internal hemorrhoids does not consider the severity of bleeding. We intended to establish a useful method for evaluating internal hemorrhoids using a colonoscope that reflected the severity of the symptoms. METHODS: Using a colonoscope in the retroflexed and forward viewing position, 104 patients with symptomatic internal hemorrhoids were evaluated based on the criteria of range, form and red color signs (RCS). Range was determined by the circumferential distribution of internal hemorrhoids and scaled from 0 to 4. Form was determined by size and scaled from 0 to 2. The presence of RCS was also evaluated. Symptoms were determined by interview and scaled from 0 to 3. Patients were treated by endoscopic band ligation (EBL) and were examined endoscopically before and 4 weeks after the treatment. RESULTS: Before the treatment, range, form and RCS were significantly correlated to bleeding (P < 0.01), and form was significantly correlated to prolapse (P < 0.05). The endoscopic classification scores at 4 weeks after EBL improved significantly (range from 3.25 +/- 0.05-0.56 +/- 0.08 [P < 0.01] and form from 2.81 +/- 0.04-0.56 +/- 0.07 P < 0.01). CONCLUSION: The new endoscopic classification of internal hemorrhoids proved to be closely correlated to symptoms, particularly bleeding, and thus highly useful in evaluating the effectiveness of the treatment.

[Pharmaceutical and pharmacological evaluation of Burow's solution (aluminum acetate solution), hospital preparation, and development of its rapid preparation method].

Burow's solution, or aluminum acetate solution, is effective in inhibiting various microorganisms including methicillin-resistant Staphylococcus aureus (MRSA) that are commonly observed in chronic suppurative otitis media. It takes several days to prepare Burow's solution using aluminum sulfate, and the pharmaceutical properties of the solution are not fully understood. In this study, the effect of storage (5 months) of Burow's solution prepared according to the Teine-Keijin Hospital manual on its pharmaceutical properties and antibacterial activities was examined. We also attempted to develop a rapid preparation method of aluminum acetate (or 1.7% aluminum) solution using two commercially available compounds of aluminum acetate basic (Al(2)O(CH(3)CO(2))(4), Al(OH)(CH(3)CO(2))(2)). The properties of Burow's solution, pH, osmolarity and antibacterial activity, were the same among different preparations and its storage for 5 months at 4 degrees C had no effect on these properties. The antibacterial potency of Burow's solution was dependent on aluminum concentration and its antibacterial potency against S. aureus and several MRSA strains was of the same magnitude. In a rapid preparation, aluminum acetate basic was mixed with appropriate amounts of tartaric acid and acetic acid, and the suspension was boiled for 2-2.5 hr until dissolved. The rapidly prepared aluminum acetate solution showed the same pharmaceutical properties and antibacterial activities as those of Burow's solution. The newly developed preparation method for aluminum acetate solution is expected to be convenient and feasible for hospital treatment of chronic suppurative otitis media.

Retroflexed endoscopic multiple band ligation of symptomatic internal hemorrhoids.

BACKGROUND: Elastic band ligation is a well-established nonoperative method for treatment of internal hemorrhoids that give rise to symptoms. This study assessed the efficacy and safety of retroflexed endoscopic multiple band ligation, a procedure that involves extensive ligation of internal hemorrhoids, and the immediately proximal normal rectal mucosa, by means of a retroflexed endoscope. METHODS: Eighty-two patients with symptoms caused by internal hemorrhoids (15, stage I; 19, stage II; 47, stage III; 1, stage IV) were treated by retroflexed endoscopic multiple band ligation. Symptoms (prolapse, bleeding, pain with defecation) were graded from 0 to 3. Range and form of the internal hemorrhoids were evaluated endoscopically. Retroflexed endoscopic multiple band ligation was performed by using a flexible endoscope with an attached band ligation device in the retroflexed position. RESULTS: A mean of 8 bands (range 4-14) were placed per treatment session. Seventy-six patients were treated in a single session, 5 in two sessions, and one in 3 sessions. Symptom and endoscopic scores improved at 4 weeks after the retroflexed endoscopic multiple band ligation: bleeding, from 1.26 to 0.53 (p<0.01); prolapse, from 1.94 to 0.5 (p<0.01); pain, from 1.03 to 0.93 (p=0.67); Goligher classification, from 2.41 to 1.09 (p<0.01); range, from 3.25 to 0.56 (p<0.01); and form, from 2.81 to 0.56 (p<0.01). Long-term response (mean follow-up 12 months, range 3-40 months) was excellent for 89% of the patients, good for 9%, and poor for 2%. No major complication was noted. CONCLUSIONS: Retroflexed endoscopic multiple band ligation is a safe and effective method for treatment for patients with symptoms caused by internal hemorrhoids.

Capillary electrophoresis of small anions in complex samples with a hollow fiber sampling inlet end.

A hollow fiber sampling inlet end of capillary electrophoresis (CE) for small ions in complex samples is described. A short piece of hollow fiber, which only permits small ions to pass through its wall, was directly connected to one end of a capillary. Small ions in complex samples were injected into the capillary through the hollow fiber by an electrokinetic method. The experimental results of CE for standard anion mixture solutions, river water, and milk samples show that the hollow fiber sampling inlet end is a simple and useful method for the CE of complex samples. Furthermore, it has been shown that the method can be used to study small anion changes during the milk storing process.

Platelet count is independently associated with insulin resistance in non-obese Japanese type 2 diabetic patients.

The aim of the present study was to investigate the relationship between platelet count and insulin resistance in non-obese Japanese type 2 diabetic patients. A total of 163 non-obese Japanese type 2 diabetic patients (112 men and 51 women, aged 36 to 84 years, body mass index [BMI] 16.2 to 26.9 kg/m(2)) were studied. In conjunction with BMI, glycosylated hemoglobin (HbA(1c)), fasting concentrations of plasma glucose and serum lipids (triglycerides, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol, and total cholesterol), and hematological parameters (platelets, white blood cell count, red blood cell count, hematocrit, hemoglobin) were measured. LDL cholesterol was calculated using the Friedewald formula. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). Univariate regression analysis showed that HOMA-IR was positively correlated to BMI (r = 0.465, P <.0001), HbA(1c) (r = 0.423, P <.0001), platelet count (r = 0.310, P <.0001), triglycerides (r = 0.277, P <.0005), white blood cell count (r =.222, P =.005), red blood cell count (r = 0.210, P =.008), hematocrit (r = 0.156, P =.047), total cholesterol (r = 0.178, P =.023), and systolic (r = 0.216, P =.011) and diastolic (r = 0.263, P =.002) blood pressure, and inversely correlated to HDL cholesterol (r = -0.312, P <.0001) level in our diabetic patients. Multiple regression analysis showed that HOMA-IR was independently predicted by BMI (P <.0001, F = 22.45), HbA(1c) (P <.0001, F = 16.15), platelet count (P <.0001, F = 10.75), and serum triglycerides (P <.0001, F = 10.47) levels, which explained 34% of the variability of HOMA-IR in non-obese Japanese type 2 diabetic patients. These results indicate that not only BMI, HbA(1c), and triglycerides levels but also platelet counts are independent predictor of insulin resistance in non-obese Japanese type 2 diabetic patients.

Cyclooxygenase-2 expression and angiogenesis in gastric hyperplastic polyp--association with polyp size.

BACKGROUND: Cyclooxygenase (COX)-2 is the rate-limiting enzyme in prostaglandin synthesis, and plays an important role in tumor enlargement. COX-2 is expressed in human gastric and colorectal tumors, and the expression increases in a tumor size-dependent manner. In the present study, we attempted to examine the COX-2 expression pattern in gastric hyperplastic polyp, a non-tumorous lesion. PATIENTS AND METHODS: Fifty-eight gastric hyperplastic polyps, obtained by endoscopic polypectomy, were immunostained with anti-COX-2 and antivascular endothelial growth factor (VEGF) antibodies. Microvessel density (MVD) was determined by von Willebrand factor immunostaining. RESULTS: In larger gastric hyperplastic polyps, COX-2 was expressed mainly on the luminal side of the polyp stroma, while it was absent in smaller polyps. A significant correlation between COX-2 immunoreactivity and polyp size was observed (p < 0.01). High VEGF expression and MVD were observed mainly in the same stromal region of the polyps where COX-2 was expressed. Both VEGF expression and MVD were also correlated with polyp size significantly (ps < 0.01). CONCLUSIONS: COX-2 expression increased in a size-dependent manner in non-tumorous hyperplastic polyps, suggesting that COX-2 expression is not necessarily linked to epithelial cell transformation. Moreover, COX-2 may participate in polyp enlargement through angiogenesis by promoting VEGF production.

Porphyromonas gingivalis infection is associated with carotid atherosclerosis in non-obese Japanese type 2 diabetic patients.

The aim of the present study was to investigate whether non-obese Japanese type 2 diabetic patients with porphyromonas gingivalis infection have atherosclerotic vascular diseases. A total of 134 non-obese Japanese type 2 diabetic patients (96 men and 38 women, aged 36 to 84 years, body mass index [BMI] 20.1 to 26.9 kg/m(2)) were studied. In conjunction with BMI, glycosylated hemoglobin (HbA(1c)), fasting glucose, and serum lipids (triglycerides, total cholesterol, high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol) were measured. LDL cholesterol was calculated using the Friedewald formula. Using high-resolution B-mode ultrasound scan, we measured intimal medial thickness (IMT) in plaque-free segments of bilateral common carotid arteries, and the mean of IMT in 2 vessels was used for the analysis. Furthermore, we calculated the degree of stenosis in plaque segments of bilateral common carotid arteries. The degree of carotid atherosclerosis was expressed as a percentage ratio between the area of plaque and that of the lumen using the formula (Lumen Area Residual - Lumen Area)/Lumem Area x 100. Both the areas were automatically measured by the system on a frozen transverse scanning plane at the site of maximal narrowing. When 2 or more plaques were present in the vessel, only that causing the greatest degree of stenosis was considered for analysis. Values represent mean+/-SEM unless otherwise stated. Immunoglobulin G (IgG) titer against porphyromonas gingivalis was 245 +/- 65 (mean +/- 2 SD) in nondiabetic healthy subjects. In contrast, there was a wide variation in IgG titer against porphyromonas gingivalis in type 2 diabetic patients studied (range, 16 to 26,800). Thus, we classified our type 2 diabetic patients into 2 subpopulations according to the value of mean +/- 2 SD (= 310) of nondiabetic healthy subjects: one with high IgG titer against porphyromonas gingivalis (>310) (1,422 +/- 408) and the other with normal IgG titer against porphyromonas gingivalis (<310) (152 +/- 10, P =.002). The populations did not differ with respect to age, sex, BMI, fasting glucose, HbA(1c), serum triglycerides, total, HDL, and LDL cholesterol levels. Although the mean IMT in plaque-free segments was not different between the 2 groups (0.73 +/-0.03 v 0.68 +/- 0.02 mm, P =.098), the degree of stenosis in plaque segments was significantly higher in the high IgG titer group (12.0% +/- 2.2%) than in normal one (5.5% +/- 1.4%, P =.009). From these results, it can be concluded that porphyromonas gingivalis infection, although still a subclinical infection, is associated with atherosclerotic vascular disease in non-obese Japanese type 2 diabetic patients.

XIB4035, a novel nonpeptidyl small molecule agonist for GFRalpha-1.

We investigated the agonistic activities of N(4)-(7-chloro-2-[(E)-2-(2-chloro-phenyl)-vinyl]-quinolin-4-yl)-N(1),N(1)-diethyl-pentane-1,4-diamine (XIB4035), at the glial cell line-derived neurotrophic factor (GDNF) family receptoralpha-1(GFRalpha-1) in Neuro-2A cells, a mouse neuroblastoma cell line which is a suitable model for investigating functions mediated through GFRalpha-1. XIB4035 concentration-dependently inhibited [(125)I]GDNF binding in Neuro-2A cells with an IC(50) of 10.4 microM. GDNF induced autophosphorylation of Ret protein, and promoted neurite outgrowth in Neuro-2A cells. XIB4035, like GDNF, induced Ret autophosphorylation in the Neuro-2A cells. Moreover, XIB4035 promoted neurite outgrowth in a concentration-dependent manner. These results show that XIB4035 may act as an agonist at GFRalpha-1 receptor complex, and mimic neurotrophic effects of GDNF in Neuro-2A cells. This is an interesting finding showing that a nonpeptidyl small molecule is capable of inducing activation of a receptor that normally bind a relatively large protein ligand such as GDNF.

C-reactive protein and insulin resistance in non-obese Japanese type 2 diabetic patients.

The aim of the present study was to investigate the relationship between C-reactive protein (CRP) and insulin resistance in non-obese Japanese type 2 diabetic patients. A total of 135 non-obese Japanese type 2 diabetic patients (96 men and 39 women, aged 36 to 83 years, with a body mass index [BMI] of 16.2 to 26.8 kg/m2) were studied. BMI, glycosylated hemoglobin (HbA(1c)), fasting concentrations of plasma glucose, serum lipids (triglycerides, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol, and total cholesterol), CRP, and fibrinogen were measured. LDL cholesterol was calculated using the Friedewald formula. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). Univariate regression analysis showed that CRP value was positively correlated to age (r = 0.218, P =.012), BMI (r = 0.239, P =.006), HOMA-IR (r = 0.397, P <.0001), triglycerides (r= 0.310, P <.005), LDL cholesterol (r= 0.179, P =.038), and fibrinogen (r = 0.371, P <.0001) levels and inversely correlated to HDL cholesterol (r = 0.174, P =.044) level in our diabetic patients. Multiple regression analysis showed that CRP was independently predicted by HOMA-IR (P<.0001, F = 11.6) and fibrinogen (P<.0001, F = 34.2), which explained 23.5% of the variability of CRP in our non-obese Japanese type 2 diabetic patients. These results indicate that insulin resistance and fibrinogen level are independent predictors of CRP in non-obese Japanese type 2 diabetic patients.

Ultrasonographically assessed carotid atherosclerosis in Japanese type 2 diabetic patients: Role of nonesterified fatty acids.

The aim of the present study was to evaluate the association of carotid atherosclerosis (intimal-medial thickness [IMT] in plaque-free segments and carotid stenosis in plaque segments) with serum nonesterified fatty acids (NEFA) in diabetic and nondiabetic patients. Fifty-one nonobese nonhypertensive Japanese type 2 diabetic patients aged 38 to 83 years (60.0 +/- 1.5 years, mean +/- SEM) and 23 age-matched (60.4 +/- 2.2 years, P =.439; range, 36 to 74 years) and sex-matched nondiabetic subjects were examined. The duration of diabetes was 9.6 +/- 1.0 years. Body mass index (BMI), blood pressure (systolic pressure, diastolic pressure), glycosylated hemoglobin (HbA(1c)), and fasting concentrations of plasma glucose, serum lipids (triglycerides, total, and high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol) and serum NEFA were measured. Using high-resolution B-mode ultrasound scan, we measured IMT in plaque-free segments of bilateral common carotid arteries, and the mean of IMT in 2 vessels was used for the analysis. Furthermore, we calculated the degree of stenosis in plaque segments of bilateral common carotid arteries. The degree of carotid stenosis was expressed as a percentage ratio between the area of plaque and that of the lumen using the formula (Lumen Area - Residual Lumen) x 100. Both the areas were automatically measured by the system on a frozen transverse scanning plane at the site of maximal narrowing. When 2 or more plaques were present in the vessel, only that causing the greatest degree of stenosis was considered for analysis. Univariate regression analyses showed that mean IMT in plaque-free segments was positively correlated with age (r =.498, P =.0004) and NEFA (r =.354, P =.0188) in type 2 diabetic patients. The degree of stenosis was positively correlated to age (r =.422, P =.0028), duration of diabetes (r =.313, P =.0268) and NEFA (r =.540, P =.0003) in diabetic patients. Other variables, including BMI and lipid profile, were not associated both with mean IMT in plaque-free segments and the degree of stenosis in plaque segments in our diabetic patients. Multiple regression analyses showed that mean IMT in plaque-free segments was independently associated with age (P =.0003, F = 15.2), which explained 26.1% of the variability of IMT in our diabetic patients. The degree of stenosis was independently predicted by NEFA (P =.0047, F = 8.9), which explained 17.2% of the variability of the carotid stenosis in our diabetic patients. In contrast, mean IMT in plaque-free segments was positively correlated to age in nondiabetic subjects (r =.450, P =.0347). There was, however, no relationship between the degree of stenosis and the variables, including age and NEFA, in nondiabetic subjects. These results indicate that the factors contributing to IMT in plaque-free segments and the degree of carotid stenosis in plaque segments are different in nonobese nonhypertensive Japanese type 2 diabetic patients. IMT in plaque-free segments was independently associated with age both in nondiabetic and diabetic subjects, whereas the serum NEFA level independently predicted the degree of stenosis in plaque segments in our diabetic patients, while not in nondiabetic subjects. Thus, NEFA is considered to be one of the new risk factors responsible for the progression of carotid atherosclerosis in nonobese nonhypertensive Japanese type 2 diabetic patients.

Relationship of regional adiposity to insulin resistance and serum triglyceride levels in nonobese Japanese type 2 diabetic patients.

The aim of this study was to investigate the relationships between insulin resistance and regional abdominal fat area, body mass index (BMI), and serum lipid profile in nonobese Japanese type 2 diabetic patients. A total of 63 nonobese Japanese type 2 diabetic patients aged 45 to 83 years were examined. The duration of diabetes was 8.4 +/- 0.8 years. BMI, glycosylated hemoglobin (HbA(1c)) levels, and fasting concentrations of plasma glucose, serum lipids (total cholesterol, high-density lipoprotein [HDL] cholesterol, and triglycerides), and serum insulin were measured. The low-density lipoprotein (LDL) cholesterol level was calculated using the Friedewald formula (LDL cholesterol = total cholesterol - HDL cholesterol - 1/5 triglycerides). Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). Computed tomography (CT) was used to measure cross-sectional abdominal subcutaneous and visceral fat areas in all the patients. Adipose tissue areas were determined at the umbilical level. Subcutaneous and visceral abdominal fat areas were 136.5 +/- 6.0 and 86.0 +/- 4.1 cm(2), respectively. Univariate regression analysis showed that insulin resistance was positively correlated with subcutaneous (r =.544, P <.001) and visceral (r =.408, P =.001) fat areas, BMI (r =.324, P =.009), HbA(1c) (r =.254, P =.001), serum triglycerides (r =.419, P <.001), and serum LDL cholesterol (r =.290, P =.019) levels and was negatively correlated with serum HDL cholesterol level (r =.254, P =.041). Multiple regression analyses showed that insulin resistance was independently predicted by the areas of subcutaneous (F = 6.76, P <.001) and visceral (F = 4.61, P <.001) abdominal fat and serum triglycerides (F = 8.88, P <.001) level, which explained 36.9% of the variability of insulin resistance. Moreover, the present study demonstrated that whereas BMI was positively correlated with visceral (r =.510, P <.001) and subcutaneous (r =.553, P <.001) fat areas, serum triglyceride level was positively associated with visceral (r =.302, P =.015), but not with subcutaneous (r =.222, P =.074) fat area. From these results, it can be suggested that (1) both subcutaneous and visceral abdominal fat areas are independently associated with insulin resistance and (2) visceral fat area, but not the subcutaneous one, is associated with serum triglyceride levels in our nonobese Japanese type 2 diabetic patients.

A report from Japan: choices of Japanese patients in the face of disagreement.

BACKGROUND: Patients in different countries have different attitudes toward self-determination and medical information. Little is known how much respect Japanese patients feel should be given for their wishes about medical care and for medical information, and what choices they would make in the face of disagreement. METHODS: Ambulatory patients in six clinics of internal medicine at a university hospital were surveyed using a self-administered questionnaire. RESULTS: A total of 307 patients participated in our survey. Of the respondents, 47% would accept recommendations made by physicians, even if such recommendations were against their wishes; 25% would try to persuade their physician to change their recommendations; and 14% would leave their physician to find a new one. Seventy-six percent of the respondents thought that physicians should routinely ask patients if they would want to know about a diagnosis of cancer, while 5% disagreed; 59% responded that physicians should inform them of the actual diagnosis, even against the request of their family not to do so, while 24% would want their physician to abide by their family's request and 14% could not decide. One-third of the respondents who initially said they would want to know the truth would yield to the desires of the family in a case of disagreement. INTERPRETATION: In the face of disagreement regarding medical care and disclosure, Japanese patients tend to respond in a diverse and unpredictable manner. Medical professionals should thus be prudent and ask their patients explicitly what they want regarding medical care and information.