Prolactin regulatory element-binding protein is involved in suppression of the adiponectin gene in vivo.

PURPOSE: Prolactin regulatory element-binding protein (PREB), a member of the WD-repeat protein family, has been recognized as a transcriptional factor that regulates prolactin promoter activity in the anterior pituitary of rats. PREB is expressed not only in the pituitary but also in various other tissues, including the adipose tissue. Previous studies have shown that PREB acts as a transcriptional regulator and suppresses the expression of the adiponectin gene in cultured 3T3L1 preadipocytes. The aim of this study was to further examine the potential role of PREB in adipose tissue in vivo. METHODS: Transgenic mice that overexpressing PREB (PREB transgenic mice) were generated. Insulin resistance was evaluated in PREB transgenic mice using glucose and insulin tolerance tests. Adiponectin expression in the adipose tissue was examined by western blot analysis and quantitative polymerase chain reaction (qPCR). The expression levels of stearoyl-CoA desaturase (Scd) and adiponectin receptor 2(ADIPOR2) were quantified by qPCR. RESULTS: Glucose and insulin tolerance tests revealed insulin resistance in PREB transgenic mice. Serum adiponectin and leptin concentrations were decreased. Adiponectin gene expression was decreased in the adipose tissue, which was confirmed by the downregulation of the adiponectin-dependent hepatic Scd gene and upregulation of the ADIPOR2 gene in the liver of PREB transgenic mice. We also found that pioglitazone, an agonist for the peroxisome proliferator-activated receptor-r, improved the insulin resistance in the PREB transgenic mice after a 10-day feeding period. CONCLUSIONS: These results demonstrated that PREB might contribute to the regulation of adiponectin gene expression in vivo.

Comparison of the effects of polysulfone and polyester-polymer alloy dialyzers on glycemic control in diabetic patients undergoing hemodialysis.

BACKGROUND: Though different high-flux dialyzers are available, there are no comparative studies on their glycemic control effects on diabetic hemodialysis (HD) patients. In this crossover study, we compared the effects of polysulfone (PS) and polyester-polymer alloy (PEPA) dialyzers. METHODS: We recruited 47 diabetic HD patients. The conventional dialyzers were replaced with PS or PEPA dialyzers and the patients were treated for 16 weeks. Subsequently, after interchanging the PS and PEPA dialyzers, the treatment continued for another 16 weeks. For each dialyzer, we analyzed the glycemic control effect and measured their clearance and reduction rates of insulin. RESULTS: The PEPA dialyzer lowered the glycated albumin (GA) levels more significantly than the PS dialyzer. While the groups exhibited no differences in metabolic parameters, the clearance and reduction rates of insulin were more significant in the PS. A significant decrease was observed in the levels of GA, fasting plasma glucose, and glycated hemoglobin in patients with lower fasting C-peptide levels (< 6.0 ng/ml). CONCLUSION: Glycemic control in diabetic HD patients is affected by the type of dialyzer used. Our results indicate that the PEPA dialyzer is more potent in controlling glycemia than the PS dialyzer in diabetic HD patients.

Clinical evaluation of plasma insulin and C-peptide levels with 3 different high-flux dialyzers in diabetic patients on hemodialysis.

AIM: Changes in plasma immunoreactive insulin (IRI) and connecting-peptide immunoreactivity (CPR) concentrations during hemodialysis (HD) were evaluated in diabetic HD patients with 3 different high-flux membranes. The removal properties of the membranes were compared. METHOD: In this prospective controlled study, 15 stable diabetic patients on HD were randomly selected for 6 HD sessions with 3 different membranes: polysulfone (PS), cellulose triacetate (CTA), and polymethylmethacrylate (PMMA). Blood samples were obtained from the blood tubing at the arterial (A) site at the beginning and end of the sixth HD session. At 60 minutes after dialysis initiation, blood samples were obtained from both the A and venous (V) sites of the dialyzer to investigate the clearance and removal properties of the membranes. RESULTS: The plasma IRI and CPR levels decreased significantly at each time point with all 3 membranes. IRI clearance with the PS membrane was significantly higher than that with the CTA and PMMA membranes. No difference was observed in the IRI reduction rate between the 3 membranes. CPR clearance and reduction rate with the PMMA membrane were lower than with the PS and CTA membranes. No significant difference was observed in serum creatinine clearance and reduction rates between the 3 membranes; however, serum urea nitrogen clearance was significantly lower with the PMMA membrane compared with the PS and CTA membranes. A significantly high beta2-microglobulin clearance and reduction rate was achieved in the order PS > CTA > PMMA. CONCLUSION: Plasma IRI and CPR are cleared by HD; their clearance rates differ with the dialyzer membranes. Plasma IRI clearance with the PS membrane is higher than that with the CTA and PMMA membranes.

Clinical investigation of the effects of pioglitazone on the improvement of insulin resistance and blood pressure in type 2-diabetic patients undergoing hemodialysis.

AIMS: Type 2 diabetes is characterized by a combination of insulin resistance, dyslipidemia, and increased blood pressure. In this study, we evaluated the clinical efficacy of pioglitazone in the treatment of diabetic patients with hypertension undergoing hemodialysis (HD). METHODS: An open-label, randomized study was performed using 40 subjects assigned to two groups: one group (pioglitazone group) was administered an add-on pioglitazone therapy (fixed dose, 30 mg) plus conventional oral antidiabetic agents, and the other group (control group) was administered conventional oral agents alone. The treatment efficacy was determined by monitoring the glycemic control and insulin resistance, which were assessed based on the homeostasis model assessment for insulin resistance (HOMA-IR). The safety of and tolerance to the drug were determined by monitoring clinical and laboratory parameters. RESULTS: Pioglitazone was effective in reducing the plasma glucose and hemoglobin A1c levels from the baseline values, beginning at 4 weeks of treatment. It was also effective in reducing the triglyceride levels. The HOMA-IR decreased significantly in the pioglitazone group, and this decrease was maintained until the last measurement, which was at 24 weeks. The systolic and diastolic blood pressure values were statistically lower in the pioglitazone group than in the control group. No serious adverse effects were observed in any of the patients. CONCLUSIONS: Pioglitazone is safe and effective for the treatment of Type 2-diabetic patients undergoing HD therapy. A daily dose of 30 mg pioglitazone is sufficient for treating HD patients, regardless of whether or not they are obese. Furthermore, pioglitazone reduced the systolic and diastolic blood pressure in our patients, and this effect requires further investigation.

The influence of hemodialysis membranes on the plasma insulin level of diabetic patients on maintenance hemodialysis.

AIM: The aim of the present study was to evaluate the alteration in plasma immunoreactive insulin (IRI) concentrations due to hemodialysis (HD) treatment by using three types of membranes in diabetic HD patients. METHOD: We recruited 20 outpatients on maintenance HD with diabetes for this crossover study. HD was performed using membranes made of cellulose triacetate (CTA), polyester-polymer alloy (PEPA), and polysulphone (PS). These membranes were used for 2 weeks (6 HD sessions) in each patient in a randomized order decided by drawing lots. Blood samples were obtained at the beginning and end of the HD session from the blood tubing at the arterial (A) site. At 60 min after the initiation of dialysis, blood samples were obtained from the blood tubing at both the A and venous (V) sites of the dialyzer. RESULTS: The plasma IRI levels decreased significantly at the sites an hour after initiating HD in all membranes. The clearance of IRI was significantly higher in the case of the PS membrane when compared with the CTA and PEPA membranes. CONCLUSIONS: It was concluded that plasma insulin is cleared by HD, and the rate differs for each membrane. Plasma insulin clearance with the PS membrane is higher than that with the PEPA and CTA membranes.

Combination therapy of pioglitazone with voglibose improves glycemic control safely and rapidly in Japanese type 2-diabetic patients on hemodialysis.

AIMS: Unfortunately, clinicians are diagnosing a growing number of patients on hemodialysis (HD) with insulin-resistant, Type 2 diabetes in Japan. While alpha-glucosidase inhibitors (alpha-GI) such as oral antidiabetic agents are indicated for Japanese diabetics on HD, pioglitazone and other PPARgamma agonists are now contraindicated. No prospective study has evaluated the use of thiazolidinediones in diabetics with end-stage renal disease (ESRD) in combination with alpha-GI. In this study we evaluated the efficacy and safety of pioglitazone in Japanese diabetics on HD. METHODS: An open-label randomized study was performed on 31 Type 2 diabetics on HD with unstable glycemic control receiving constant doses of voglibose. The patients were randomly assigned to two groups: a combination therapy group (pioglitazone group) administered pioglitazone (fixed dose 30 mg) plus voglibose, and a monotherapy group (control group) administered voglibose alone. The efficacy of the treatments was determined by monitoring glycemic control (plasma glucose and HbA1c) and insulin resistance. Insulin resistance was assessed using the homeostasis model assessment for insulin resistance (HOMA-R). Safety and tolerance were determined by monitoring clinical and laboratory parameters. RESULTS: The pioglitazone was effective in reducing plasma glucose and HbA1c from the baseline levels from Week 4 onward. It was also effective in reducing triglycerides. HOMA-R decreased significantly at 4 weeks in the pioglitazone group, and the decrease continued up to the last measurement at Week 12. Systolic and diastolic blood pressures at 4 weeks were statistically lower in the pioglitazone group than in the control group. No serious adverse effects such as hypoglycemia, liver impairment or rhabdomyolysis were observed in any of the patients. CONCLUSIONS: Pioglitazone was safe and effective as a treatment for diabetics on dialysis therapy. The 30 mg daily dose of pioglitazone was sufficient for Japanese HD patients, obese and nonobese alike. The combination therapy of pioglitazone with voglibose will add to the list of first-line drug treatments for glycemic control in uremic Type 2 diabetes.

Immunoglobulin D myeloma presenting as an extraosseous soft tissue tumor.

We report a 69-year-old man who suffered an extraosseous tumor of immunoglobulin D myeloma (lambda type) in the shoulder girdle, mimicking a primary soft tissue sarcoma. The tumor was isointense with adjacent muscle on T1-weighted MR images, and hyperintense on T2-weighted images. No continuity with the neighboring bone was noted. After administration of gadolinium, the central part of the tumor showed marked contrast enhancement. Although the tumor showed a complete response to the initial chemotherapy, the patient died of the disease 31 months after its initial manifestation. Several bone marrow aspirations and biopsies of the ilium and sternum had shown no increase in plasma cells (range 0.6-1.2%) until the disease became advanced 19 months after its initial manifestation.

Intravascular ultrasound imaging before and after angioplasty for stenosis of arteriovenous fistulae in haemodialysis patients.

BACKGROUND: Complications of haemodialysis vascular access have emerged as a major cause of patient morbidity. Intravascular ultrasound imaging is a new technical modality providing visualization of the vessel lumen and wall structure in a cross-sectional fashion. Percutaneous transluminal angioplasty has long been used in the treatment of stenoses of arteriovenous fistulae. However, there is no detailed quantitative information on the stenotic lesion and the morphological change by angioplasty. METHODS: Intravascular ultrasound studies were performed in 40 haemodialysis patients with 63 stenoses in arteriovenous fistulae who had percutaneous transluminal angioplasty. The patients were qualitatively and quantitatively evaluated for echogenic patterns and morphological changes before and after angioplasty. RESULTS: Morphological plaque features in stenotic lesions were classified as 37 soft (58%), five hard (8%), 20 mixed (32%), and one calcified sites. Plaque fractures after angioplasty were detected in 45/63 (71%) instances. The lumen cross-sectional area was found to be dilated approximately threefold (from 3.8+/-2.4 to 11.1+/-4.5 mm(2)) and the external elastic membrane cross-sectional area was dilated approximately twofold (from 11.1+/-5.3 to 19.8+/-8.1 mm(2)) after angioplasty. CONCLUSION: These results indicate that intravascular ultrasound allows both qualitative and quantitative assessments of arteriovenous fistulae in haemodialysis patients. The results further suggest that the mechanism of expansion of arteriovenous fistulae stenoses by percutaneous transluminal angioplasty involves stretching of the vessel wall as well as plaque fractures.

Recurrent chondromyxoid fibroma of the thoracic spine 30 years after primary excision: case report and review of the literature.

We report a case of late recurrence of chondromyxoid fibroma (CMF) arising in a thoracic vertebra in an 11-year-old male. This was treated by curettage, and 30 years later, the patient noticed shoulder pain and leg weakness. A recurrent mass appeared at the same site in the spinous process of T6. The histologic features of the recurrent tumor were similar to those of the primary lesion. A total of 38 cases of CMF of the vertebra have been reported. Only 3 of 38 previously reported vertebral CMF recurred. Tumors recurred 2 years after operation in 2 cases, and 7 years after operation in 1 case.

[The influence of correction of acidosis on plasma level of branched-chain amino acids in chronic hemodialysis patients].

Seven patients undergoing chronic hemodialysis three times a week and whose plasma bicarbonate concentration on predialysis was consistently under 18 mmol/l due to bicarbonate dialysis (BCD), were treated with BCD for 2 weeks, then switched to acetate-free biofiltration (AFB) for 8 weeks. In both periods, the same high flux dialyzer (AN69HF) was used. The treatment time, dialysate flow rate and blood flow rate were kept constant in each patient during both periods. Plasma bicarbonate concentration (HCO3-), serum urea nitrogen (SUN), serum creatinine (Cr) and plasma amino acids concentrations (AA) were measured before dialysis and KT/V was calculated on the 2nd days of the last week in both periods. HCO3- on AFB was significantly higher than that on BCD (16.4 +/- 0.9 vs 19.9 +/- 1.8 mmol/l; p < 0.05). SUN on AFB was significantly lower than that on BCD even though the dialysis schedule and dietary content were not changed (84.7 +/- 3.7 vs 76.6 +/- 3.8 mg/dl; p < 0.05). TP, Cr and KT/V were not significantly different. Plasma total amino acid concentration (TAA) and plasma essential amino acid concentration (EAA) were not significantly different in both periods. In contrast, plasma branched-chain amino acid concentrations (BCAA) on AFB were significantly higher than that on BCD (313.5 +/- 44.3 vs 390.3 +/- 50.7 mumol/l; p < 0.05). Plasma BCAA concentrations, valine (VAL), leucine (LEU) and isoleucine (ILE), were significantly higher on AFB than that on BCD, respectively (p < 0.05). These findings suggest that optimal correction of the metabolic acidosis in chronic hemodialysis patients by AFB leads to a significant increase in plasma BCAA concentration.

Effect of the hydroxyl group on the oxidative cleavage (beta-oxidation) of steroidal side chain for bile acid biosynthesis in rat liver homogenate.

Mono-, di-, tri-, and tetrahydroxy-5 beta-cholestan-26-oic acids were incubated with rat liver homogenate (800 x g supernatant and light mitochondrial fraction) to study substrate specificity in the side-chain cleavage reaction (beta-oxidation) of bile acid biosynthesis. The C27-intermediates (5 beta-cholest-24-en-26-oic acids and 24-hydroxy-5 beta-cholestan-26-oic acids) in beta-oxidation and the corresponding C24-bile acids were quantitatively determined by capillary gas chromatography. Monohydroxy-5 beta-cholestan-26-oic acid was not converted into C24-bile acid. Di- and trihydroxy-5 beta-cholestan-26-oic acids were effectively transformed into the C27-intermediates and C24-bile acids. Tetrahydroxy-5 beta-cholestan-26-oic acids were also converted into C27-intermediates and corresponding C24-bile acids. The intermediate 24-hydroxy-5 beta-cholestan-26-oic acids could not be detected in the products by incubation with the light mitochondrial fraction. The total specific activity of protein in the light mitochondrial fraction for the production of C27-intermediates and C24-bile acids was higher than that of 800 x g supernatant solution. The effects of the number and the position of hydroxyl groups on the side-chain degradation are discussed.

Neuropathological findings in the cerebro-oculo-facio-skeletal (Pena-Shokeir II) syndrome.

An autopsy case is described of an infant with cerebro-oculo-facio-skeletal (COFS) (Pena-Shokeir II) syndrome who died of pneumonia at the age of 5 months, and the pathology of the CNS in this case and the cases in literature were reviewed. Neuropathological examination revealed a partial defect of the corpus callosum, lobulation of the caudate nucleus and putamen, polymicrogyria in the parietal lobes and neuronal heterotopia in the cerebral and cerebellar white matter. The migration disorders suggest that the onset starts in the early fetal period.

Characterization of the binding of nuclear envelope precursor vesicles and chromatin, and purification of the vesicles.

The binding of nuclear envelope precursor vesicles and chromatin was characterized by using an in vitro system constituted from a Xenopus egg extract and demembranated Xenopus sperm chromatin. The results of binding studies in the presence of salts, urea, and a chelator showed that the binding involves an ionic interaction. Chemical modification studies suggested that a protein(s) in the vesicles, which is responsible for the binding with chromatin, has essential lysine, histidine, and methionine residues. The vesicle protein could not be extracted from vesicles with 1 M KCl, 2 M urea, or 0.1 M Na2CO3, suggesting that it is an intrinsic membrane protein. The protein was denatured with 8 M urea and 0.1 M Na2CO3, and could be renatured by incubation at 23 degrees C, suggesting that the native conformation of the protein is important for the binding. Affinity purification of nuclear envelope precursor vesicles was achieved by binding to chromatin and dissociation with 0.24 M NaCl. The vesicle fraction thus obtained exhibited the ability to form nuclear envelope on incubation with chromatin in Xenopus egg cytosol without any other membrane fraction. These results suggested that there is a nuclear envelope precursor vesicle population containing both a chromatin targeting protein and vesicle fusion machinery.

Primary biliary cirrhosis sera recognize not only gp210 but also proteins of the p62 complex bearing N-acetylglucosamine residues from rat liver nuclear envelope. Anti-p62 complex antibody in PBC.

We have recently observed reactivity of primary biliary cirrhosis (PBC) sera with several proteins bearing N-acetylglucosamine residues from rat liver nuclear envelopes. The aim of this study was to characterize the reactive antigens. Sera from 31 patients with PBC, 30 with rheumatoid arthritis (RA) and 30 with Sjögren's syndrome (SS) were examined. Rim-like immunofluorescence staining was observed in 15 of 31 (48%) sera from patients with PBC, in 1 of 30 with RA and in 1 of 30 with SS. Upon immunoblotting using preparations of whole rat liver nuclear envelopes and their Triton X 100-KCl extract as antigen sources, a 200 kDa protein band was observed in 9 of sera with PBC. Furthermore, upon immunoblotting using the wheat germ aggulutinin-bound fraction of rat liver envelope as antigen, 62, 60 and 54 kDa protein bands corresponding to components of the p62 complex in the nuclear pore complex (Kita et al. Biochem. 113, 377-382) were observed in 7, 5 and 6 samples respectively, of the 31 PBC sera. Our data suggest that PBC sera recognize not only the 210 kDa protein but also the p62 complex proteins.

[Operative removal of esophageal leiomyosarcoma: a case report].

This is a case report of 56-year-old man complaining of dysphasia. Upon admission, his chest X-ray film revealed medium amount of fluid accumulation in the right pleural space. Cytological examination of the aspirated fluid revealed nothing particular. Preoperative radiological examination including esophagogram, CT and MRI demonstrated cystic appearance of mass lesion, measuring approximately 5 cm in size located in posterior aspect of the lower portion of the mediastinum. Upon operation, it was found that a tumor with pedunculated connection to the esophageal muscle layer, suspecting diagnosis of leiomyoma of the esophagus. Then, tumor was removed together with the part of esophageal muscle. Postoperative pathology reported leiomyosarcoma of the esophagus with low grade malignancy. We added no esophagectomy. He made uneventful recovery without no sign of recurrence of the malignancy, 4 years after the surgery.

Inheritance of seed α-amylase inhibitor in the common bean and genetic relationship to arcelin.

The inheritance of seed α-amylase inhibitor in the common bean and the genetic relationships among the variants and six arcelin variants in the common bean were investigated by crossing between accessions containing different αAI and arcelin variants. All seed proteins in parental, F1 and F2 seeds from the crosses were examined by Western-blot analysis. All F1 seeds gave combined αAI banding patterns from parents on the blotting membranes. The segregation of F2 seeds for αAI variants indicated that the polypeptides of αAI variants were inherited as single co-dominant units. Moreover, αAI and arcelin behaved as a single block in crosses, indicating a close linkage relationship between the genes controlling these proteins.

Variation of seed α-amylase inhibitors in the common bean.

Variation of seed α-amylase inhibitors was investigated in 1 154 cultivated and 726 non-cultivated (wild and weedy) accessions of the common bean, Phaseolus vulgaris L. Four α-amylase inhibitor types were recognized based on the inhibtion by seed extracts of the activities of porcine pancreatic α-amylase and larval α-amylase and larval α-amylase of the Mexican bean weevil, Zabrotes subfasciatus Boheman. Of the 1 880 accessions examined most (1 734) were able to inhibit porcine pancreatic α-amylase activity, but were inactive against the Z. subfasciatus larval α-amylase; 41 inhibited only the larval α-amylase activity, 52 inhibited the activities of the two α-amylases, and 53 did not inhibit the activity of either of the α-amylases. The four different inhibitor types were designated as αAI-1, αAI2, αAI-3, and αAI-0, respectively. These four inhibitor types were identified by the banding patterns of seed glycoproteins in the range of 14-20 kDa by using SDSpolyacrylamide gel electrophoresis. Additionally, four different banding patterns were recognized in accessions with αAI-1, and were designated as αAI-1a, 1b, 1c, and 1d. Two different patterns of the accessions lacking an α-amylase inhibitory activity were identified and designated as αAI-0a and αAI-0b. The largest diversity for seed α-amylase inhibitors was observed in non-cultivated accessions collected from Mexico where all eight inhibitor types were detected. The possible relationships between the variation of seed α-amylase inhibitors and bruchid resistance are discussed.

Effects of recombinant human erythropoietin (rHuEPO) on nutritional status of hemodialysis patients: investigation of direct anabolic effects of rHuEPO.

To investigate whether the nutritional improvement achieved by recombinant human erythropoietin (rHuEPO) treatment is the result of anemia correction with rHuEPO or the direct anabolic effects of rHuEPO per se, nutritional assessment was performed in 2 studies (study I and II) on hemodialysis (HD) patients. Nutritional assessment included blood biochemistry determinations, anthropometric measurements, daily protein intake (DPI) and dialysis efficiency. In study I, 5 HD patients who had not been given rHuEPO and had a hematocrit (Hct) of < or = 25%, were administered rHuEPO at the initial dose of 96.2 U/kgBW. Nutritional assessment of these patients was performed before rHuEPO treatment and every 4 weeks until the 24th week after rHuEPO treatment. In study II, the same nutritional assessment as in study I except for DPI, was performed in 2 groups with the same Hct level and dialysis regimen; an EPO group (n = 8) previously given rHuEPO (88.2 +/- 13.7 U/kgBW, 25.8 +/- 2.5 mos) and a non-EPO group (n = 8) not given rHuEPO. In study I, the mean Hct level was significantly increased 4 weeks after rHuEPO treatment (23.3 +/- 0.6 to 26.9 +/- 0.9%). However, the nutritional parameters and dialysis efficiency were nearly constant over 24 weeks, suggesting either the absence of a short-term direct anabolic effect of rHuEPO or masking of such an effect due to general condition improvement by anemia correction with rHuEPO. In study II, no significant differences in nutritional assessment were confirmed between the groups, suggesting that a long-term direct anabolic effect of rHuEPO may not exist and nutritional improvement may result from correction of anemia with rHuEPO.(ABSTRACT TRUNCATED AT 250 WORDS)